This article was originally published in a journal published by Elsevier, and the attached copy is provided by Elsevier for the author’s benefit and for the benefit of the author’s institution, for non-commercial research and educational use including without limitation use in instruction at your institution, sending it to specific colleagues that you know, and providing a copy to your institution’s administrator. All other uses, reproduction and distribution, including without limitation commercial reprints, selling or licensing copies or access, or posting on open internet sites, your personal or institution’s website or repository, are prohibited. For exceptions, permission may be sought for such use through Elsevier’s permissions site at: http://www.elsevier.com/locate/permissionusematerial
Developmental Biology 299 (2006) 310 – 329 www.elsevier.com/locate/ydbio
Review
co
Markus Friedrich ⁎
py
Continuity versus split and reconstitution: Exploring the molecular developmental corollaries of insect eye primordium evolution Department of Biological Sciences, Wayne State University, 5047 Gullen Mall, Detroit, MI 48202, USA Department of Anatomy and Cell Biology, Wayne State University, School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201, USA
al
Received for publication 30 January 2006; revised 31 July 2006; accepted 12 August 2006 Available online 16 August 2006
Abstract
pe
rs
on
Holometabolous insects like Drosophila proceed through two phases of visual system development. The embryonic phase generates simple eyes of the larva. The postembryonic phase produces the adult specific compound eyes during late larval development and pupation. In primitive insects, by contrast, eye development persists seemingly continuously from embryogenesis through the end of postembryogenesis. Comparative literature suggests that the evolutionary transition from continuous to biphasic eye development occurred via transient developmental arrest. This review investigates how the developmental arrest model relates to the gene networks regulating larval and adult eye development in Drosophila, and embryonic compound eye development in primitive insects. Consistent with the developmental arrest model, the available data suggest that the determination of the anlage of the rudimentary Drosophila larval eye is homologous to the embryonic specification of the juvenile compound eye in directly developing insects while the Drosophila compound eye primordium is evolutionarily related to the yet little studied stem cell based postembryonic eye primordium of primitive insects. © 2006 Elsevier Inc. All rights reserved. Keywords: Insect eye development; Evolution of development; Drosophila; Tribolium; Schistocerca; Gene network; Selector gene; Metamorphosis
r's
Introduction
Au
th o
In recent years, the interest of Drosophila eye developmental genetics has shifted from studying cell fate specification in the differentiating retina to the specification of the adult compound eye primordium. The redirection of research focus was initiated by the keystone discovery that the Drosophila eyeless (ey) gene encodes the homolog of the transcription factor Pax-6, which has similar roles in early eye primordium development of “mice, men and flies” (Gehring, 2002; Quiring et al., 1994). Subsequent studies unraveled a network of highly conserved genes, which control the determination of the Drosophila compound eye primordium (Pappu and Mardon, 2004; Silver and Rebay, 2005). One of many surprising outcomes in these studies was that the adult eye primordium is not determined in the embryo, but later during postembryogenesis ⁎ Department of Biological Sciences, Wayne State University, 5047 Gullen Mall, Detroit, MI 48202, USA. Fax: +1 313 577 6891. E-mail address:
[email protected]. 0012-1606/$ - see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.ydbio.2006.08.027
(Kenyon et al., 2003; Kumar and Moses, 2001a). This finding overturned the traditional assumption of an embryonic time point of adult eye determination based on the results from mosaic analysis that had demonstrated the existence of separate eye and antenna precursor cell populations in the embryo (Baker, 2001; Kumar and Moses, 2001a; Postlethwait and Schneiderman, 1971). The postembryonic timing of adult eye determination in Drosophila was also surprising since the compound eye of primitive insects begins to differentiate in the embryo implying embryonic determination of the compound eye primordium as ancestral situation (Friedrich, 2003). This discrepancy raises several questions: What is the reason for the delay of adult eye determination in Drosophila? Which modifications of development facilitated this delay? Is the gene network, which orchestrates the postembryonic determination of the Drosophila eye primordium, identical to the network controlling compound eye determination in the embryos of primitive insects? The present review addresses these issues by reminding that not only the development of the adult but also that of the larval
M. Friedrich / Developmental Biology 299 (2006) 310–329
co
pe
rs
on
al
The diversity of insect compound eye primordium morphogenesis Primordia are identified as fields of cells that become morphologically distinct and can be traced to provide the cellular material for a specific organ. Often, and so in the case of the eye, primordium formation is associated with a transition from cuboidal to columnar cell organization leading to thickened placode or disc-like areas. Consistent with their common evolutionary roots, the compound eye primordia of primitive and holometabolous insects emerge as placode-like derivatives in the lateral head ectoderm. The temporal and spatial context of this process, however, differs in significant ways as do embryonic and postembryonic contributions to the adult compound eye.
anlagen and nymphal compound eye primordium thus derive from a shared precursor cell population in the head neuroectoderm. Formation of the embryonic eye lobes begins when the founder neuroblasts of the outer optic lobe anlagen segregate by delamination from the neuroectodermal population of prospective eye primordium cells (Roonwal, 1936). The eye primordium in a strict sense has been identified as placode-like area in the posterior margin of the eye lobe ectoderm (Roonwal, 1936). Starting at about midway of embryogenesis, the eye lobe ectoderm transforms into the nymphal retina in the wake of a differentiation front, which initiates at the posterior eye placode margin, and strongly resembles the morphogenetic furrow of the Drosophila eye disc (Fig. 1a) (Dong et al., 2003; Friedrich and Benzer, 2000). Driven by the proliferation of the optic lobe anlagen neuroblasts, the embryonic eye lobes gain dramatic size and develop into prominent lateral protrusions (Fig. 1a). Accommodating for the volume increase, the eye lobe ectoderm expands through uniform cell division. Subsequent to the initiation of retinal primordium differentiation, additional domains of highly concentrated cell division produce retinal precursor cells. These are located anterior and posterior to the grasshopper morphogenetic furrow and correspond to the first and second mitotic wave in the differentiating Drosophila compound eye retina (Friedrich and Benzer, 2000). Thus, following the onset of differentiation, the developmental events in grasshopper embryonic compound eye primordium closely parallel those in the postembryonic compound eye primordium of Drosophila (Friedrich, 2003).
py
eye in Drosophila is evolutionarily related to compound eye development in primitive insects. The underlying transition from continuous visual system development in primitive insects to biphasic visual system development in higher insects is still documented in a variety of juvenile and adult eye development modes of extant insects. With this background, the molecular genetics of Drosophila adult and larval eye development is reviewed as well as data available on the molecular regulation of embryonic compound eye development in lesser derived insects. The comparison reveals that the molecular data are consistent with morphological evidence, which suggests that the Drosophila larval eyes develop from ancestral embryonic compound eye primordia. The postembryonic compound eye primordium of Drosophila is proposed to be derived from the stem-cell population, which facilitates persistent retinal differentiation in the juvenile instars of primitive insects.
311
r's
The embryonic eye primordium in primitive insects: eye lobe and eye placode
Au
th o
The most ancestral mode of eye primordium morphogenesis has been conserved in directly developing insects where adult body patterning is largely completed during embryogenesis. This includes ametabolous insects, like silverfish and bristletail, and hemimetabolous species, such as dragon flies, grasshoppers, cockroaches, and true bugs (Bate, 1978; Friedrich, 2003; Meinertzhagen, 1973). In all of these groups, the embryonic eye primordium gives rise to the compound eye of the first instar of the juvenile or nymphal form (Fig. 1b). Recent descriptions of the embryonic development of the nymphal compound eye have been produced for grasshopper and cricket (Dong et al., 2003; Dong and Friedrich, 2005a; Friedrich, 2003; Friedrich and Benzer, 2000; Inoue et al., 2004). In these models of hemimetabolous development, the nymphal compound eye primordia form within more inclusive embryonic head compartments: the eye lobes (Fig. 1a). The eye lobes derive from the lateral neuroectoderm of the embryonic cephalon. Besides the compound eye retina, the eye lobes also give rise to two visual components of the central nervous system, medulla and lamina, which together constitute the outer optic lobe neuropils (Fig. 1a) (Dong and Friedrich, 2005a; Roonwal, 1936). Outer optic lobe
The postembryonic eye primordium in non-holometabolous insects: terra incognita between proliferation and differentiation zone With completion of nymphal head morphogenesis in the late grasshopper embryo, the progressive retinal differentiation of the eye lobe transforms into a standing zone of differentiation at the frontal margin of the nymphal compound eye (Fig. 1b). The cellular material necessary to maintain retinal differentiation is drawn from within an anterior rim of mitotic cells (Anderson, 1978). In the grasshopper Schistocerca gregaria this region has been described as proliferation zone (Fig. 1b) (Bodenstein, 1953; Nowel and Shelton, 1980). The proliferation zone was proposed to represent a direct derivative of the embryonic eye primordium (Bodenstein, 1953). While the operational correspondence is evident, important differences exist. Most significantly, the proliferation zone must contain cells with stem-cell properties that sustain persistent cell proliferation through nymphal development. Conceivably, competence restriction and transcriptional specification of the cells produced in the stem cell zone is equivalent to that of the cell population in the undifferentiated embryonic eye lobe ectoderm. Successive stages of ommatidium formation gradually merge with the differentiated retina in the differentiation zone (Anderson, 1978). Most of the adult compound eye in primitive insects develops from the postembryonic stem-cell reservoir during development of the nymph.
M. Friedrich / Developmental Biology 299 (2006) 310–329
pe
rs
on
al
co
py
312
Au
th o
r's
Fig. 1. Embryonic and postembryonic eye primordia in fruit fly, beetle and grasshopper. In all panels dorsal is up and anterior to the right except for the dorsal view of the Drosophila larval head skeleton in panel h. (a) Confocal projection of lateral grasshopper embryonic head at 40% of embryonic development. The eye lobes (elo) have gained considerable size and encompass outer optic lobe (ola) anlagen, inner optic lobe (ila) anlagen, and the differentiating anlagen of the retina (ret). mf = morphogenetic furrow, man = mandible, ant = antenna, pro = procephalon. (b) Polarized light image of frontolateral view of third instar grasshopper nymphal compound eye indicating the posterior region of embryonic origin region or embryonic cap (ec), two vertical strips of ommatidia that have been formed in the nymph (1 + 2), and locations of the differentiation (d) and proliferation (p) zones fronting the nymphal eye. gen = gena, ver = vertex, oce = ocelli. (c) Same as in panel b but at final, i.e. fifth nymphal instar, documenting the effect of expansive eye development in the grasshopper nymphal eye. Two more vertical coloration stripes (3 + 4) have been formed. (d) Confocal projection of Tribolium lateral embryonic head at early germ band retraction stage. Inlet shows overview of embryo with area of focus indicated by box. Position of the reduced Tribolium eye lobe indicated by hatched outline. Optic lobe anlage and larval eye anlage (ley) are separated by invagination cleft (arrowhead). Lbr = labrum. (e) Lateral view of Tribolium larval head at early last instar showing position of larval eyes. Dorsal (dst) and (vst) ventral stemmata are positioned closely posterior of the larval antenna, mandible and maxillary (max) appendages. (f) Lateral view of resting stage Tribolium larval head. Larval eyes have been withdrawn from perspective towards the brain. Photopigment expressed in early differentiating photoreceptors indicates initiation of retinal differentiation in the adult eye placode (eyp) (indicated by hatched outline). (g) Lateral view of Drosophila embryonic head labeled by in situ hybridization for the segmentation marker wingless (brown) and the photoreceptor marker glass (blue). Larval eye differentiation has initiated at the ventral tip of the optic placode (op). The dorsal sector of the optic placode, develops in the outer and inner optic lobe anlagen. Lab = labium, max = maxilla, mid = midline. (h) Dorsal view of dissected Drosophila cephalopharyngeal head skeleton (cep) showing relative size and position of Bolwig organs (bol) detected by GFP reporter gene expression (pseudocolored red) in pGMR-GFP flies. The artificial GMR enhancer activates transcription specifically in photoreceptor cells (Hay et al., 1994). (i) Differential interference contrast image of the third instar larval Drosophila eye-antennal imaginal disc. Distribution of selected organ or cuticle region anlagen based on Haynie and Bryant (1986) indicated by hatched outlines for the disc proper (dpr) and solid dark grey lines for the peripodial membrane (per). Lpo = lower postorbital region, pge = postgena, sc = shingle cuticle lateral bristle.
Embryonic eye primordium of holometabolous insects: the larval eye anlage The transformation of a highly diverged juvenile body plan into that of the adult is the defining feature of holometabolous insects. This process of complete metamorphosis initiates in the last larval instar and finalizes in the pupa, the resting stage preceding the hatching of the adult.
Larval body plan diversification is particularly impressive in the visual system. Unlike the elaborate adult compound eyes, which are formed in the pupa, the eyes of the larva usually consist of small, ocelli-like photoreceptor concentrations called stemmata (Fig. 1e) (Gilbert, 1994). As studies in beetles have shown, the larval eyes originate from lateral embryonic head ectoderm in close association with the optic neuropils (Fig. 1d) (Heming, 1982). This situation is
M. Friedrich / Developmental Biology 299 (2006) 310–329
py
co
al
Postembryonic eye primordium in higher flies: the eye disc The evolutionary transition from eye placode to true eye imaginal disc type of adult eye primordium development is well documented in the higher Diptera (Melzer and Paulus, 1989). During the evolution of cyclorrhaphan flies, the exoskeletal head capsule of the eucephalic larva internalized thereby transforming into the cephalopharyngeal skeleton known from Drosophila (Fig. 1h). The evolution of larval acephaly (headlessness) enforced the development of adult organs from primordia that are independent of the larval body plan, known as imaginal discs. These “secondary morphogenetic fields” represent the developmental solution to allowing larval and adult morphology evolve freely from mutual developmental constraints (Svacha, 1992; Truman and Riddiford, 2002). The Drosophila adult eye develops in the eye-antennal imaginal disc, which forms by invagination from the embryonic head ectoderm (Haynie and Bryant, 1986; Wolff and Ready, 1993). The eye-antennal disc derives from cells of several head compartments including the labral, antennal, intercalary and all gnathal segments (Younossi-Hartenstein et al., 1993). Consistent with its multi-segmental origin, the eye-antennal disc gives rise to diverse regions of the adult head, including antenna, ocelli and cuticle areas surrounding the eye (Fig. 1i) (Haynie and Bryant, 1986). Yet, despite multi-primordial origin and fate, the early eye-antennal disc shows no morphological signs of primordium specification in the first instar larva. It resembles a small sac of morphologically equivalent ectodermal cells (Cho et al., 2000; Younossi-Hartenstein et al., 1993). Morphogenetic hallmarks of postembryonic growth and development include:
rs
Postembryonic eye primordium in primitive holometabolous insects: the eye placode
referred to as eye disc (Champlin and Truman, 1998). The transient, postembryonic formation of an epidermal pocket is, however, fundamentally different from embryonic imaginal disc development in more derived species such as Drosophila (see below) (Green et al., 1993; Svacha, 1992). Differentiation of the retina initiates in the posterior margin of the eye placode and progresses in anterior direction headed by the morphogenetic furrow (Fig. 1f) (Champlin and Truman, 1998; Egelhaaf, 1988; Friedrich et al., 1996). The events leading to eye placode formation in lesserderived holometabolous insects are poorly documented. Embryonic precursor cells, which contribute to the adult eye placode, have not been mapped. The earliest developmental stage at which adult eye primordium cells could thus far be identified on morphological grounds is the first instar larva in mosquitoes (White, 1961). It is therefore unclear if the adult eye anlage is already specified and determined in the embryo to persist into the larva or activated later by spatial cues within the lateral head epidermis of the larva.
on
virtually identical to the embryonic development of the first instar nymphal compound eye in non-holometabolous insect (Fig. 1a) (Friedrich, 2003; Roonwal, 1936). There are, however, significant morphogenetic differences. In concert with juvenile eye size reduction, holometabolous insects evolved small larval optic neuropils (Green et al., 1993; Heming, 1982). Due to the shift of adult outer optic lobe anlagen growth into postembryogenesis, the embryonic eye lobes are not very pronounced (Fig. 1d) (Heming, 1982; Liu and Friedrich, 2004). A second difference resides in the mode of separation of optic lobe anlagen and larval eye primordium cell fields. In the Holometabola, the optic lobe anlage segregates as a cell sheet by invagination, as opposed to delamination of single cells in the developing eye lobe of primitive insects. Invagination of the optic lobe anlage has been described for Drosophila and lesser derived beetle species (Green et al., 1993; Heming, 1982; Liu and Friedrich, 2004; Ullmann, 1966). It is likely a shared derived trait of the Holometabola (Friedrich et al., in press). Setting morphogenetic differences aside, the origin and segregation of optic lobe and eye anlagen from a common embryonic precursor cell field, the visual anlage, is a shared aspect of holometabolous and non-holometabolous insects.
313
Au
th o
r's
pe
Primitive representatives of holometabolous insects form most adult organ primordia in the same way as non-holometabolous insects during embryogenesis. This is reflected in the highly differentiated head capsule of eucephalic larvae, which are typical for basal species in all major holometabolous orders (Fig. 1e) (Friedrich, 2003). Still in strong resemblance to the head morphology of hemimetabolous insect nymphs, the eucephalic larval head is fully encapsulated by a cuticle exoskeleton and equipped with antennae and mouthpart appendages. The larval head appendages derive from the embryonic primordia (Fig. 1d), and serve as templates for a second round of growth and differentiation into adult organs during metamorphosis. This patterning strategy of redeployment with modification, however, does not apply to the visual system. Instead of continuing stemmatal development, the differentiation of the adult retina initiates de novo in the lateral larval head epidermis (Fig. 1f) (Friedrich and Benzer, 2000). In some species, the primordia of the adult eye can be recognized as fields of columnar cells (White, 1961). Similar fields of condensed, diploid cells have been reported in the lateral head of moth and beetle larvae (Friedrich et al., 1996; Marshall, 1928; Monsma and Booker, 1996). Highlighting the cell morphological similarity to the embryonic eye primordium of non-holometabolous insects, the adult eye primordium is usually referred to as eye placode (Marshall, 1928). In species with large compound eyes, such as the tobacco horn moth Manduca sexta, the early development of the eye placode is associated with massive cell proliferation that leads to delamination from the exoskeletal cuticle (Champlin and Truman, 1998). At this stage, the inward folded placode is also
(I) Specification of a sheet of squamous cells, the peripodial membrane, which covers the eye disc proper. (II) Separation of antenna and eye disc regions by the second larval instar.
314
M. Friedrich / Developmental Biology 299 (2006) 310–329
primordium. The highly integrated process of adult eye and head cuticle development in the Drosophila eye-antennal disc stands in stark contrast to head and visual system morphogenesis in hemimetabolous and eucephalic holometabolous insects.
(III) Initiation of retinal differentiation at the posterior margin of the eye disc during the early third larval instar (Figs. 1i and 2b) (Cho et al., 2000; Wolff and Ready, 1993). The compound eye primordium forms at the posterior margin of the eye disc proper (Haynie and Bryant, 1986). Before the onset of differentiation, the future borders of head cuticle and eye primordia are morphologically not clearly pronounced in the eye disc. Moreover, since the undifferentiated eye primordium is not of defined placode character, initiation and anterior progression of the morphogenetic furrow are the first histological manifestations of the eye
py
Origin and homology of larval and adult eyes of holometabolous insects
th o
r's
pe
rs
on
al
co
To understand the evolutionary origin of visual system development in higher insects, one needs to turn to scorpion flies. Representatives of the scorpion fly family Panorpidae
Au
Fig. 2. Temporal and cellular dynamics of eye development in directly developing and holometabolous insects. Hemimetabola (Schistocerca): ommatidia develop continuously during embryogenesis and juvenile instars to contribute to the final adult compound eye. Mitotic activity persists during juvenile instars in a proliferation zone in front of the juvenile eye. The adult eye consists of both embryonic and postembryonic ommatidia. Holometabola (Panorpa, Tribolium and Drosophila): visual system development is split into two phases. Differentiation of larval eyes completes in the embryonic phase. No differentiation or cell division occurs in front of the larval eyes during postembryogenesis. The larval eyes of the scorpion fly Panorpa exhibits compound eye like architecture documenting the evolutionary origin of holometabolous insect larval eyes from compound eyes. The larval eyes of Tribolium and Drosophila are reduced to stemmata. While the larval eyes of Tribolium remain peripheral in the larval head, the Drosophila Bolwig organs are withdrawn inside the larval head. At the end of postembryogenesis, the larval eyes of Tribolium and Drosophila are further withdrawn into the brain. In Drosophila and Tribolium, the relocated larval eyes have been shown to dedifferentiate into extraretinal photoreceptors. The adult stage fate of Panorpa larval eyes has not yet been described. The second phase of holometabolous visual system development begins with the initiation of adult compound eye development in the last larval instar. The adult eye consists therefore entirely of postembryonic ommatidia. The situation in Drosophila is further complicated by the development of the adult eye from eye-antennal imaginal disc tissue, which is physically distinct from the juvenile epidermis. During embryogenesis, the eye-antennal disc separates from the epidermis by invagination. During metamorphosis, the eye-antennal imaginal disc derivatives completely replace the larval epidermis. Apoptosis of larval epidermis indicated by dotted outlines. Color code of cellular components: Grey = epithelial cells which persist from the embryo into adult, black = epithelial cells which are disposed during postembryogenesis, dark blue = cone cells, brown = pigment cells, orange cones = embryonic photoreceptor cells, red cones = postembryonic photoreceptor cells, filled orange circles = internalized larval eyes. Progressing morphogenetic forrow represented by forward pointing arrowhead. Lack of documentation of a morphogenetic furrow assumed to be formed during embryonic eye development in Panorpa is indicated by question mark. Same applies to the unknown fate of the larval eyes in Panorpa. Red stop sign indicates developmental arrest proposed by Paulus (1989).
M. Friedrich / Developmental Biology 299 (2006) 310–329
on
al
co
py
the nymphal compound eye in primitive insects (Liu and Friedrich, 2004). Moreover, the two stemmata of the flour beetle larva were found to develop by fusion of five initial embryonic photoreceptor cell clusters. This process appears to recapitulate the fusion of ancestral ommatidia previously hypothesized to underly the evolution of the more compact larval visual organs (Fig. 2) (Paulus, 1986). Combined with the insights from Panorpa, these data consolidate the homology of stemmata and first instar nymphal compound eyes. The Drosophila larval eyes, better known as Bolwig organs, are particularly interesting in this context. Virtually any ancestral traces documenting a relation to compound eye ommatidia have been eradicated during evolution of these extremely reduced structures (Fig. 2). The Bolwig organs consist of a bundle of 12 cell photoreceptor cells attached to the cephalopharyngeal head skeleton inside the larva (Fig. 1i) (Bolwig, 1946; Green et al., 1993). The light collecting cell membrane compartments of the photoreceptors are organized in simple lamellar stacks, in contrast to the microvillar rhabdomeres that are formed in adult ommatidia as well as in the stemmata of lesser derived Holometabola (Melzer and Paulus, 1989). Also, the morphogenesis of the Drosophila larval eyes is highly derived. Due to reduction and inversion of the head capsule, and the lack of optic neuropils in the acephalic larva, the Drosophila embryo does not form morphologically compartmentalized head lobes, as they are prominent in the embryos of primitive insects. It has been noted that the initial morphology of the single cell cluster from which the Bolwig organ forms exhibits similarities to early stages of ommatidial cell cluster formation in the developing adult eye (Green et al., 1993). Yet strongest evidence for evolutionary relatedness of the Drosophila Bolwig organs to compound eye ommatidia has been found at the level of the gene. The same rhodopsin visual pigment gene family paralogs are expressed in Bolwig organ and adult compound eye photoreceptors [Rh5 and Rh6], whereas a different paralog, Rh2, is expressed in the ocelli, the prominent single lens accessory visual organs of the adult (Helfrich-Forster et al., 2002; Malpel et al., 2002; Pichaud and Deplan, 2001; Pollock and Benzer, 1988; Yasuyama and Meinertzhagen, 1999). The expression of Rh5 and Rh6 orthologs in the stemmata and adult ommatidia of lepidopteran species suggests that this aspect of the Drosophila visual system is ancestral (Briscoe and White, 2005). As will be discussed in detail, there is also a significant overlap between the gene network regulating Drosophila Bolwig organ specification and that coordinating adult compound eye specification (Daniel et al., 1999; Suzuki and Saigo, 2000). In summary, three lines of evidence support the evolution of holometabolous insect larval eyes from ancestral compound eye ommatidia:
Au
th o
r's
pe
rs
retained the most ancestral larval eyes known in the Holometabola. Panorpa larvae possess 25–45 ommatidia-strong compound eyes as main visual organs (Gilbert, 1994; Steiner, 1930). It is virtually identical to that of the later formed, functionally independent adult compound eye (Fig. 2) (Paulus, 1979). The compound eye organization of the Panorpa larval eyes is highly reminiscent of the situation in nymphal instars of non-holometabolous insects, which hatch with fully functional compound eyes (Fig. 2) (Ando and Suzuki, 1977). However, important differences exist. While nymphal eyes continue to expand during postembryogenesis by differentiation of new ommatidia from the anterior growth zone, the number of ommatidia in the larval eyes of Panorpa does not increase following embryogenesis (Paulus, 1989). At completion of postembryogenesis, the larval compound eyes of Panorpa are replaced by newly formed adult compound eyes (Paulus, 1989). This contrasts with the inclusion of all embryo born ommatidia to the adult compound eye in non-holometabolous insects (Fig. 2) (Friedrich, 2003; Meinertzhagen, 1973). The scorpion fly visual system represents a highly informative intermediate state of insect visual system development (Paulus, 1989). It documents that the larval eyes of holometabolous insects evolved from ancestral ommatidia. More specifically, the larval eyes are homologous to those ommatidia in primitive insects, which differentiate in the embryo and constitute the first nymphal instar compound eye (Fig. 2) (Paulus, 1989). Further support for this relationship comes from the adult fate of the larval photoreceptors. In Drosophila, the larval photoreceptors persist in the imago as extra-retinal sense organs, which contribute to diurnal rhythm entrainment (Helfrich-Forster et al., 2002; Mazzoni et al., 2005). This extraordinary functional reutilization is very likely conserved in other Holometabola. Relocalization of the larval eyes into the adult brain has been reported in different orders including Lepidoptera, Neuroptera and Coleoptera (Fleissner et al., 1993; Friedrich et al., in press; Hagberg, 1986; Ichikawa, 1991). Thus, despite morphological and functional divergence, the larval eyes of the Holometabola remain functional in the adult just like their nymphal eye counterparts do (Fig. 2). In most Holometabola outside the genus Panorpa, larval eyes experienced extensive evolutionary modification. Pervasive trends are the fusion of ommatidia into stemmata and the reduction of cuticular lens, lens cells and pigment cells (Gilbert, 1994). Examples of secondarily refined vision exist as well. The highly resolving, lens eye-like stemmata of predatory tiger beetle larvae incorporate thousands of photoreceptor cells (Friedrichs, 1931). Due to the increasing degree of modification, the homology of larval stemmata and nymphal compound eyes is often difficult to establish on the basis of morphological similarity. It is, however, still reflected in the similarities between larval eye morphogenesis and the embryonic origin of nymphal compound eyes in directly developing species (Heming, 1982). Comparative analysis in Tribolium using molecular markers for photoreceptor cell differentiation and head segmentation confirmed that the larval eye primordium corresponds to the embryonic primordium of
315
(I) morphological conservation of ommatidial cell architecture in the larval eyes of scorpion flies, (II) similarities in the morphogenesis of larval and nymphal eyes, and (III) shared gene activities in the larval and adult eyes of Drosophila.
316
M. Friedrich / Developmental Biology 299 (2006) 310–329
Shared aspects of the Drosophila adult and larval eye specification gene networks
Recognizing the evolutionary ancestry of insect larval eyes is critical for understanding key differences of visual system development in insects. In non-holometabolous species, ommatidia that were formed in the embryo persist in the nymphal and later adult eye. Second, the nymphal compound eye continuously expands via addition of newly developing ommatidia at its anterior margin following the morphogenetic furrow progression driven-phase of retina differentiation in the embryo. The adult eye of non-holometabolous insects is therefore a composite of embryonic ommatidia in its posterior partition and nymphal ommatidia in its anterior partition (Fig. 2). In holometabolous insects, visual system development consists of two separate phases each of which produces discrete, life cycle stage-specific organs. The first phase occurs during embryogenesis and generates the larval eyes. After an intermission of “developmental silence” a second phase generates the adult stage specific compound eyes in the late larva and during the pupal resting phase. Based on temporal correspondence in development and function, the larval eyes of holometabolous insects are homologous to the first instar compound eyes and, likewise, the contribution of the latter to the posterior region of the adult eye in primitive insects. The adult eye of holometabolous insects, on the other hand, is homologous to the anterior partition of the adult compound eye in primitive insects, which forms during nymphal development. It follows that the development of larval eyes is homologous to the embryonic development of nymphal compound eyes in primitive insects. The postembryonic phase of visual system development in holometabolous insects is, in a strict sense, homologous to the expansive mode of postembryonic compound eye development in the nymphs of primitive insects. This interpretation of insect eye development is consistent with a model of visual system evolution in the Holometabola that has been deduced by comparative inference (Fig. 2). As pointed out by Paulus (1989), the situation in scorpion flies suggests that the first step in the evolutionary transformation from continuous to discontinuous development consisted in transient repression of eye development in the ancestor of holometabolous insects. This modification split the continuously developing ancestral visual organ into not only temporally but also spatially separate partitions. Subsequent structural and functional diversification of the larval eyes could occur due to their functional independence from the adult compound eye. The transient arrest model of the evolution of biphasic visual system development is consistent with the neuroendocrine model of the evolution of insect metamorphosis, which holds that the larval body plan of holometabolous insects evolved by developmental arrest and functional extension of an ancestrally embryonic stage, the pronymph, into postembryogenesis (Truman and Riddiford, 1999). It also provides the key for understanding the origin of postembryonic determination of the Drosophila compound eye. It suggests that the adult eye primordium of holometabolous insects is a silenced primordium in its ancestral form.
One prediction from the transient arrest model is that the molecular mechanisms regulating precursor cell competence restriction should be very similar during embryonic and postembryonic eye primordium determination in higher insects, given the origin from a single ancestral eye. This can be tested by comparing the mechanisms orchestrating the postembryonic specification of the Drosophila compound eye, which are well understood (Dominguez and Casares, 2005; Pappu and Mardon, 2004; Silver and Rebay, 2005), with that specifying the larval eye anlage in the Drosophila embryo. Such comparative analysis reveals a core of genetic interactions, which are shared between the two networks (Friedrich, in press):
co
py
The transient arrest model of biphasic visual system development
Au
th o
r's
pe
rs
on
al
(I) Central event in the specification of Drosophila larval and adult eyes is the precipitation of a transcription factor complex, which incorporates the products of the essential eye selector genes eyes absent (eya) and sine oculis (so) (Fig. 3c) (Bonini et al., 1993, 1997; Cheyette et al., 1994; Rayapureddi et al., 2003; Serikaku and O'Tousa, 1994; Tootle et al., 2003; Zimmerman et al., 2000). In vitro evidence shows that Eya has binding affinity for So (Pignoni et al., 1997). Consistent with the Eya:So eye specification transcription factor complex model, eya and so show strongly overlapping expression patterns in the embryonic visual system and the eye disc. In the embryo, both genes are activated early in the dorsal head neuroectoderm, where the expression domain of so is considered to outline the visual anlage (Chang et al., 2001). After segregation of the visual anlage into different primordia of the visual system, both genes continue to be coexpressed in the outer optic lobe and the differentiating larval eye but not in the eye antennal disc (Fig. 3a) (Chang et al., 2001). During the second larval instar, eya and so expression initiates in the eye disc. The slightly earlier onset of eya expression is considered to be the first molecular manifestation of the compound eye primordium (Chang et al., 2001; Chanut and Heberlein, 1997; Kenyon et al., 2003). In the differentiating eye disc of the third instar larva, eya and so continue to be coexpressed in a wide region of undifferentiated tissue ahead of the morphogenetic furrow (Bessa et al., 2002). This region has been termed pre-proneural domain (PPN) reflecting an increased capacity of cells to enter neural development (Bessa et al., 2002; Greenwood and Struhl, 1999; Hayashi and Saigo, 2001). The expression of eya and so persists into the morphogenetic furrow and the differentiating retina, where eya and so continue coexpression in the photoreceptor cells (Bonini et al., 1993; Cheyette et al., 1994). Reduction of eya or so expression both anterior and posterior of the morphogenetic furrow results in patterning defects (Pignoni et al., 1997). Consistent with this, so was identified as direct activator of the Runx type transcription factor gene lozenge (lz), which contributes to the regulation of ommatidial cell type specification
317
th o
r's
pe
rs
on
al
co
py
M. Friedrich / Developmental Biology 299 (2006) 310–329
Au
Fig. 3. Comparison of the Drosophila larval and adult eye determination gene networks. (a) Schematic description of larval eye primordium development. Three progressive stages of embryonic visual system development are shown from dorsal perspective. Areas labeled red indicate cell populations expressing eya in the visual system. BOL = Bolwig organ, EAD = eye-antennal imaginal disc, OLAi = inner optic anlage, OLAo = outer optic anlage, VIS = visual anlage. (b) Morphogenesis and spatial control of adult compound eye specification in the Drosophila eye-antennal imaginal disc. Red indicates eya expressing areas. AF = antennal field, AP = antennal primordium, EP = eye primordium, EF = eye field, MF = morphogenetic furrow. (c) Overlay schematic of gene interactions in the larval and adult Drosophila eye primordium. Context specificity of genes or gene interactions is color coded as indicated in reference box. Proteins assumed to form complexes are indicated by background enclosures.
posterior to the morphogenetic furrow (Flores et al., 1998; Yan et al., 2003). Based on their requirement in specification and differentiation of the retina, eya and so have been classified “early retinal genes” (Desplan, 1997). The likewise critical requirement of eya and so for the development of the larval photoreceptors, in which both genes continue to be coexpressed during differentiation as well, underlines the
similarity of early retinal gene function in the larval and adult eye (Suzuki and Saigo, 2000). The transcription co-factor dachshund (dac) may also be a shared component of the early retinal transcription factor complex (Mardon et al., 1994). Like So, Dac has been found to be able to bind Eya (Chen et al., 1997). Dac, a direct target gene of so, is expressed in the PPN domain, the morphogenetic furrow, and in a limited region
M. Friedrich / Developmental Biology 299 (2006) 310–329
al
co
py
Diptera like Drosophila underwent extreme reduction leading to the loss of an entire protocerebral neurectoderm expression domain (Liu et al., in press). Drosophila may thus not be the best model to investigate ancestral patterning mechanisms of wg during embryonic visual system development. Nonetheless, the spatial relationship between the differentiating Bolwig organ and neuroectodermal wg expression renders it possible that wg has the same repressive effects on photoreceptor development as in the eye disc (Fig. 1g) (Liu et al., in press). As will be discussed below in detail, the situation in lesser-derived holometabolous species with eucephalic larvae, such as Tribolium, documents that the function of wg in larval eye patterning is largely identical to its function during early compound eye patterning. (IV) The third signaling pathway with similar roles in coordinating specification and differentiation of the larval and adult eye primordia is that initiated by Hh (Hedgehog). In the second instar eye disc, Hh becomes expressed in a small posterior rim of cells to deliver a permissive signal for the initiation of dpp expression and consequently eya (Dominguez and Hafen, 1997; Pappu et al., 2003). Once the morphogenetic furrow moves across the disc, hh is transiently expressed in differentiating photoreceptor cells immediately posterior to the furrow. This co-migrating Hh signal supports maintenance of furrow progression, and coordinates neuronal specification, spacing, and cell proliferation (Dominguez and Hafen, 1997). Activation of Dpp by Hh in the furrow generates a long range eye selector gene induction signal (Greenwood and Struhl, 1999). Furrow movement also depends on activation of Raf signaling by Hh (Dominguez, 1999; Greenwood and Struhl, 1999). In the furrow, Hh initiates neuronal development by activating expression of ato (Dominguez, 1999). The same signal is also required for the reduction of ato expression from all furrow cells to that of R8 photoreceptor founder cells (Dominguez, 1999). In the embryo, Hh promotes visual system development in multiple ways. One of its roles, the initiation of ato expression in the Bolwig organ primordium, is directly equivalent to Hh function in the morphogenetic furrow. Hh is a critical and sufficient signal for larval eye development. Reduction of Hh signaling leads to loss of larval eye due to its importance in the activation of ato (Suzuki and Saigo, 2000). Increasing Hh signaling leads to the increase of ato-positive cells in expense of optic lobe tissue. This transformation may be due to repression of tailless (tll) which is a crucial selector of optic lobe fate (Daniel et al., 1999).
Au
th o
r's
pe
rs
posterior of the furrow (Bessa et al., 2002; Pappu et al., 2005). Dac is essential for initiation of retinal differentiation and normal ommatidial patterning, but, unlike eya and so, not absolutely essential for photoreceptor differentiation (Mardon et al., 1994; Pignoni et al., 1997). Posterior to the furrow, dac may add to the regulation of photoreceptor of subtype specification potential (Hayashi and Saigo, 2001). Expression and function of dac in the embryonic visual system is less documented. Dac is not expressed in the early visual anlage like so and eya but is expressed later in the optic lobe anlage (Kumar and Moses, 2001b). Expression and possible requirement in the Bolwig organ precursor cells has not yet been specifically addressed but seems a strong possibility, considering the overall correspondence of early retinal gene involvement in the embryonic and adult visual system. (II) In both the embryonic and the adult visual system, the initiation of eya and so transcription is triggered by the BMP-2/4 homolog decapentaplegic (dpp) (Chang et al., 2001; Curtiss and Mlodzik, 2000). In the embryo, Dpp ligand is expressed in the dorsal blastoderm midline. In the eye-antennal imaginal disc, dpp expression appears at the posterior margin of the eye disc during the second larval instar, quickly followed by initiation of eya and so in this area (Curtiss and Mlodzik, 2000). Dpp signaling is thus a critical initiator of both Drosophila larval and compound eye primordium specification (Fig. 3). (III) As in many other situations, Wingless (Wg) signaling functions as an antagonistic force of Dpp during eye primordium patterning. The reach of anteriorlyexpressed Wg into the eye-antennal disc is controlled by transcriptional repression by Dpp diffusing from the posterior margin of the disc (Chanut and Heberlein, 1997; Pignoni and Zipursky, 1997; Royet and Finkelstein, 1997; Wiersdorff et al., 1996). While Dpp induces retina determination and differentiation from the posterior margin by activating eya and so expression, Wg represses the early retinal genes (Burke and Basler, 1996; Heberlein et al., 1993; Ma and Moses, 1995; Royet and Finkelstein, 1997; Treisman and Rubin, 1995; Wiersdorff et al., 1996). Wg also suppresses neuronal differentiation by inhibiting the expression of the proneural genes atonal (ato) and daughterless (da) in the morphogenetic furrow (Fig. 3) (Cadigan et al., 2002; Niwa et al., 2004). The repressive effect of Wg on retinal determination and differentiation is part of a circuit, which generates eye primordium precursor cells through maintenance of uncommitted proliferating tissue. Consistent with this model, Wg signaling also stimulates cell proliferation (Baonza and Freeman, 2002; Lee and Treisman, 2001). The role of Wg patterning in the visual system of the Drosophila embryo has not yet been investigated. The comparison with wg expression in directly developing insects and eucephalic holometabolous species reveals that the expression of wg in the ocular segment of higher
on
318
Larval and adult eye specification gene network differences in Drosophila Since the morphogenetic events leading to the formation of larval and adult eye primordia in Drosophila differ
M. Friedrich / Developmental Biology 299 (2006) 310–329
substantially, it is not unexpected to find the conserved gene network aspects imbedded in a periphery of divergent regulatory interactions (Fig. 3). Nonetheless, the number and quality of differences between the larval and adult eye specification gene networks are notable for the shared evolutionary origin of both visual organs.
co
r's
pe
rs
on
al
(IV)
(V)
Au
th o
does occur later in the optic lobe and in the segregating eyeantennal disc anlage of the gastrulating embryo (Fig. 3a) (Chang et al., 2001; Czerny et al., 1999). These data show that toy does not enforce ey expression in the early visual anlage, demonstrating situation-dependent differences in eye selector gene cross-regulation. Adding to the contrast between the larval and adult eye specification networks is the fact that the visual anlagen expression of so also occurs in the absence of toy (Halder et al., 1998). This suggests that the expression of so in the visual anlage is not dependent on toy as it is in the eye-antennal disc. While the effect of toy or ey on embryonic dac or eya has not been reported yet, the results for so suggest that the retinal determination complex initiates independently of Pax-6 genes in the visual anlage. Significant differences exist with regards to how Hh function is processed at the target gene level during larval and adult eye development. While dpp and eya are the primary targets of Hh regulation in the eye disc, the activation of eya is independent of Hh in the embryo (Fig. 3) (Pappu et al., 2003; Suzuki and Saigo, 2000). Likewise, dpp is activated independently of hh in the visual system, and both signaling pathways do not appear to engage in mutual regulation (Chang et al., 2001). It is further noteworthy that Hh promotes specification of all components of the visual anlage including the eye-antennal imaginal disc. Ectopic signaling leads to enlargement of the eye-antennal imaginal disc, the optic lobe anlagen and the Bolwig organ, while reduction of Hh signaling is followed by loss of ato expressing larval eye primordium cells and ey expressing eye-antennal imaginal disc cells (Chang et al., 2001; Pappu et al., 2003; Suzuki and Saigo, 2000). It is unclear, however, if expression of ey in the eye-antennal imaginal disc is directly Hh dependent or if the loss of ey is a secondary consequence of primordium loss. Nonetheless, while the induction of ato as the final outcome of Hh signaling activity is shared, different network interactions lead up to this event. A further deviation from the eye-antennal disc paradigm is implied by the lack of optix expression in the embryonic visual system (Seimiya and Gehring, 2000). Optix is thus a third ey target in the eye disc which is not activated in the embryonic visual system. While it still remains to be tested if optix is indeed essential for compound eye specification, as suggested by its ectopic eye induction activity, it seems likely that Bolwig and compound eye development differ in their dependence on optix. Two further selector genes, the zinc finger transcription factor teashirt (tsh) and the homeobox transcription factor homothorax (hth) have, like optix, important functions during regional specification of the compound eye primordium, but are not expressed in the embryonic visual system (Bessa and Casares, 2005; Bessa et al.,
py
(III) (I) The most dramatic difference between the larval and adult eye determination gene networks is in the involvement of the Pax-6 transcription factor ey and its closely related paralog twin of eyeless (toy) (Czerny et al., 1999; Quiring et al., 1994). Both genes are essential for compound eye primordium formation and sufficient to induce ectopic compound eye structures in imaginal disc areas outside the eye field (Czerny et al., 1999; Halder et al., 1995). The induction of eye specification by ey and toy occurs via a transcriptional activation cascade, which, coordinated by Hh and Dpp signaling input, targets the initiation of early retinal genes (Fig. 3c). Being essential for activation of ey in the early eyeantennal imaginal disc, toy represents the topmost initiator of the compound eye specification cascade (Fig. 3) (Czerny et al., 1999). In synergy with ey, toy also directly activates downstream genes, as has been shown for so (Halder et al., 1998; Niimi et al., 1999; Punzo et al., 2002). Ey has also been identified as direct activator of the eye selector gene optix and eya (Ostrin et al., 2006). The induction of eya in the second instar larval eye disc also relies on the onset of Dpp signaling, in addition to the much earlier initiated expression of ey (Kenyon et al., 2003). One of the roles of ey in the eye disc is therefore that of a compound eye primordium competence factor. Unlike the early retinal genes, ey and toy are expressed from the beginning in the eye-antennal imaginal disc and throughout the eye disc field thus also encompassing non-retinal organ primordia (Fig. 4) (Kenyon et al., 2003). Remarkably, the larval eyes of Drosophila have been reported to develop independently of ey and toy (Suzuki and Saigo, 2000). Ato expression and pioneer axon development of the Bolwig organ exhibit no detectable deficiencies in nullo 4 embryos, which lack the fourth chromosome, where ey and toy are located (Halder et al., 1998; Suzuki and Saigo, 2000). This situation is unexpected, considering that the involvement of Pax-6 is a widely conserved aspect of eye development. It also implies that the activation of eya and so can occur in the absence of ey and toy mediated competence restriction in the larval eye primordium. (II) The Pax-6 independent development of the Drosophila larval eyes correlates with further regulatory departures from the compound eye specification network. In the blastoderm embryo, toy is expressed in a wide field of the head neuroectoderm, encompassing the visual anlage (Czerny et al., 1999). Despite the activating effect of toy on ey in the early eye disc, ey is not expressed in the toyexpressing embryonic visual anlagen field. Ey expression
319
(VI)
M. Friedrich / Developmental Biology 299 (2006) 310–329
al
co
py
(VIII) The adult eye specific involvement of hth is complemented by embryo specific antagonists of eye selector genes. The Hox-3 homolog zerknuellt (zen) is induced by maximal Dpp signaling levels in the amnioserosa and in the midline neuroectoderm of the dorsal embryo. Zen represses eya and so in the dorsal embryonic midline region of the initially contiguous visual anlage (Chang et al., 2001; Ferrier and Akam, 1996; Rushlow et al., 1987). This step implements the separation of the visual system into a paired structure (Chang et al., 2001). Neither dpp nor zen has been implicated with negative regulation of eye selector gene expression in the eye antennal imaginal disc during normal development. (IX) The orphan nuclear receptor tailless (tll) may be a second embryo-specific antagonist of larval eye primordium determination (Pignoni et al., 1990). Its expression domain in the anterior blastoderm embryo encompasses the visual anlage. During grastrulation, tll expression persists in protocerebrum and outer optic lobe anlagen, but clears from cells contributing to the larval and adult eye anlagen (Daniel et al., 1999; Rudolph et al., 1997). The differential expression of tll in the segregating anlagen of the visual system reflects a critical selector gene function. Loss of tll transforms optic lobe precursors into larval photoreceptors, while ectopic expression switches the fates of Bolwig organ and midline cells into that of optic lobe cells (Daniel et al., 1999). Tll is thus necessary and sufficient for the specification of outer optic lobe anlagen fate in the visual anlage. A possible role of tll during adult eye primordium development has not yet been investigated. In situ hybridization experiments suggest that tll is expressed in the anterior eye-antennal imaginal disc, where its expression may extend from domain I into the PPN domain consistent with a possible role in the repression of retinal differentiation (Chang et al., 2001).
Au
th o
r's
pe
rs
2002; Friedrich, in press; Kurant et al., 1998; Rieckhof et al., 1997). Coexpression of tsh, ey and hth characterizes domain II anterior of the PPN domain in the eye disc. Domain II cells are considered in a proliferating state “predisposed to develop into eye” (Fig. 4) (Bessa et al., 2002). Biochemical evidence suggests that Hth cooperates with Ey and the homeobox gene Tsh by forming a transcription factor complex, the function of which is to maintain the anterior eye field uncomitted and proliferating (Fig. 3) (Bessa et al., 2002). In combination with Hth and Ey, Tsh acts as a repressor of eya and dac expression, consistent with the hypothesized transcription factor complex formation (Bessa et al., 2002). Tsh is also a transcriptional activator of the eye fate antagonist hth in this context (Bessa et al., 2002). Differently from hth, tsh is also expressed in the PPN domain. In this region, tsh provides, like ey, competence for the activation of eya, so and dac in response to Dpp signaling (Bessa and Casares, 2005). Thus tsh is involved in both the maintenance of tissue proliferation and the regulation of eye primordium competence. This translates into the dependence of compound eye development on transient expression of tsh (Bessa and Casares, 2005). Interestingly, neither tsh nor its paralog tiptop is expressed in the visual system ruling out similar functions during larval eye primordium specification (Fasano et al., 1991; Laugier et al., 2005). (VII) When coexpressed with ey and tsh, hth functions as a repressor of retinal development (Bessa et al., 2002). Ectopic hth expression replaces prospective compound eye with head cuticle, whereas loss of hth activity leads to ectopic compound eye formation (Pichaud and Casares, 2000). The eye fate repressing effect of hth is mediated by the inhibition of early retinal genes like eya and dac (Bessa et al., 2002). Hth is thus a critical regulator of both eye versus head cuticle specification and of antenna fate determination. Hth is selectively expressed in the anterior-most region of the eye disc (domain I), and in domain II with ey and tsh (Fig. 4). However, expression data suggest that hth has no comparable regional specification function in the embryonic head. Expression is not detected before onset of head involution in the embryonic head region (Kurant et al., 1998; Rieckhof et al., 1997). At a later stage, hth is expressed in a complex pattern in the developing brain, which may include the invaginating larval eye (Kurant et al., 1998). Also the localization of Extradenticle (Exd), an obligatory cotranscription factor of Hth (Aspland and White, 1997), points against a early patterning function of Hth in the embryonic visual system. Exd protein is by default cytosolic, but becomes nuclear if bound to a cotranscription factor partner like Hth. Exd localization in the embryonic head is cytosolic, consistent with the assumption that hth is not active in this part of the embryo (Aspland and White, 1997).
on
320
Molecular control of embryonic compound eye specification in primitive insects It is straightforward to interpret shared aspects of the Drosophila larval and adult eye specification networks as the outcome of shared evolutionary ancestry and developmental constraint. More than one cause, however, must be considered as potential explanation for differences between the two networks. The derived morphogenesis of both the larval and adult visual system raises the possibility of unique modifications of ancestral pattering mechanisms in either of these processes. If larval and adult eye specification programs trace back to a single ancestral gene regulatory network, they should differ to the same degree from ancestral network aspects still conserved in primitive insects. It is, however, also possible that there are ancestral differences between retinal specification in the embryonic neuroectoderm, and retinal specification in the nymphal compound eye growth zone. Detangling the contribution of ancestral and more recently accumulated changes to the
M. Friedrich / Developmental Biology 299 (2006) 310–329
Au
th o
r's
pe
rs
on
al
co
Eye selector genes Pax-6 genes have been implicated in visual system development of many vertebrate and invertebrate species (Gehring, 2002). Expression of Pax-6 genes in the embryonic visual primordia of lesser-derived insects is therefore expected. Unfortunately, little information is yet available regarding the expression or function of Pax-6 in insect species outside Drosophila. A PCR-based search for ey and toy homologs recovered single Pax-6 gene homologs from lesser derived insects including grasshopper (Czerny et al., 1999). More recently, two Pax-6 genes representing orthologs of ey and toy based on gene tree analysis have been reported from a milliped species (Prpic, 2005). The milliped Pax-6 genes are expressed in the central nervous system in patterns very similar to those in Drosophila (Prpic, 2005). Expression is also detected in the ocular segment. However, due to the high degree of visual organ reduction in millipeds, few conclusions can be drawn regarding visual system patterning. Ongoing work in the red flour beetle Tribolium castaneum identifies orthologs of both ey and toy (Yang and Friedrich, unpublished; Weller, Damen and Klingler, personal communication). Knockdown experiments show that, unlike in Drosophila, both larval and adult eye development is sensitive to Pax-6 gene reduction in Tribolium. Orthologs of toy and ey have also been isolated from grasshopper (Dong and Friedrich, unpublished). In this directly developing species, toy is expressed in the undifferentiated anterior field of the embryonic compound eye primordium reminiscent of ey expression in the Drosophila eye-antennal imaginal disc. In combination, these preliminary data indicate an involvement of Pax-6 genes in the specification of the juvenile eyes of lesser derived insects. This implies that the independence of Bolwig organ development from toy and ey is a derived situation in Drosophila. The most thorough analysis of eye selector gene expression in a non-holometabolous insect has thus far been carried out for the homolog of dac in the bispotted cricket Gryllus bimaculatus (Inoue et al., 2004). Consistent with the Drosophila adult eye primordium determination paradigm, cricket dac is expressed in the embryonic eye placode during both formation and differentiation. Similar expression of dac has been reported in the embryonic eye of a second hemimetabolous insect, the milkweed bug Oncopeltus fasciatus (Angelini and Kaufman, 2004). However, embryonic RNAi mediated knockdown of dac in the milkweed bug has no obvious impact on compound eye
development, while causing expected leg appendage patterning defects (Angelini and Kaufman, 2004). Considering the preliminary nature of negative evidence, the results from RNAi mediated knockdown experiments allow only tentative conclusions regarding a non-essential role of dac in the embryonic eye of primitive insects. It is noteworthy, however, that in mouse homozygous dach-1 knockout animals develop normal eyes despite dach-1 expression in the lens (Davis et al., 2001; Donner and Maas, 2004). The second mouse dac homolog dach-2 is not expressed in the eye, precluding genetic redundancy (Heanue et al., 1999). These data raise the possibility of a deeper divergence of dac function between Drosophila and other animal systems. The expression of so and eya orthologs has been studied in grasshopper embryos (Dong and Friedrich, 2005a). As in Drosophila, grasshopper so and eya show strong overlapping expression patterns in the visual system. The onset of coexpression in the visual anlage of lateral embryonic head is already observed before eye lobe formation, and it persists into the differentiating anlage (Fig. 4). The eya and so co-expressing cell area of the eye lobes gives rise to the lamina compartment of the outer optic lobe and to the compound eye placode. Unlike dac in the cricket, so and eya remain strongly expressed in the differentiating grasshopper retina. Overall, the regulation of early retinal genes in the embryonic visual system of directly developing insects corresponds well to the roles of eya, so and dac in the conserved core network of Drosophila eye specification gene interactions (Fig. 3c). No published reports exist yet on optix orthologs in nonholometabolous insects. Expression and function of a homolog of tsh, however, has been studied in milkweed bug (Herke et al., 2005). Uniform tiptop/tsh mRNA expression is detected throughout much of the early embryonic head after germband elongation. Yet, similarly to the results with Drosophila dac, phenotypic consequences of embryonic knockdown are limited to leg appendage development. A potential lack of tiptop/tsh involvement in the developing embryonic eye primordium of primitive insects appears possible but needs to be examined further.
py
divergence of visual organ specification networks in Drosophila is difficult. Nonetheless, if the divergence of embryonic and postembryonic eye specification mechanisms is evolutionarily old, one would expect the molecular specification of the Drosophila Bolwig organ to show more similarity to embryonic compound eye development in primitive insects than the molecular control of Drosophila compound eye development. The data emerging from comparative studies of embryonic compound eye development in primitive insects offer a first entry point to approach this issue.
321
Eye fate antagonistic selector genes The compound eye fate antagonistic gene hth has been studied in a variety of primitive insects. Published expression patterns of hth in the embryo of the milkweed bug suggest low expression levels in the dorsal head epithelium (Angelini and Kaufman, 2004). Consistent with a conserved antennal fate selector gene function, hth mRNA-depleted embryos lack antennal appendages due to either defective appendage formation or deletion of the entire antennal head segments. However, embryonic RNAi knockdown does not affect compound eye size, as might be predicted from the hth phenotypes in Drosophila (Pichaud and Casares, 2000). The lack of detectable compound eye abnormalities in hth knockdown affected milkweed bug nymphs needs to be interpreted with the same caution as in the case of dac and tsh. Further support for a lack of hth involvement during embryonic eye
M. Friedrich / Developmental Biology 299 (2006) 310–329
al
co
py
stage embryo (Chang et al., 2001). As already pointed out, dpp is also strongly co-expressed with zen in the precursor tissue of the extra-embryonic serosa surrounding the germband (Dearden and Akam, 2001). This coexpression persists into the most peripheral germband cells, the leading edge cells (Dong and Friedrich, 2005a). Similar dpp expression patterns have been reported in cricket and flour beetle, consistent with a conserved role of dpp in dorsal body wall patterning (Niwa et al., 2000; Sanchez-Salazar et al., 1996). Initially, the dpp expressing leading edge cells are closely associated with the developing eye lobes. Once the eye lobes are fully formed, the visual primordia lose contact with dpp expressing leading edge cells. No dpp transcripts are detected in the embryonic compound eye primordium of grasshopper suggesting lack of Dpp signaling pathway activation at this stage (Friedrich and Benzer, 2000). This situation contrasts with the continuous and strong expression of dpp in the Drosophila eye-antennal disc before and during retinal differentiation (Masucci et al., 1990). Also unlike in Drosophila, dpp is absent from the morphogenetic furrow in the grasshopper after onset of retinal differentiation (Friedrich and Benzer, 2000). Homogenous low dpp expression levels are detected in the undifferentiated eye lobe ectoderm anterior of the morphogenetic furrow, which has selector gene expression similarities to the PPN domain of the Drosophila eye-antennal disc (Fig. 4) (Friedrich and Benzer, 2000). The grasshopper data can be reconciled with the conserved role of dpp in the Drosophila eye specification gene networks, if one assumes that extraembryonic Dpp induces eya and so from a distance. Consistent with its dual role in Drosophila, high levels of Dpp may participate in specifying extraembryonic fate via zen in the necklace cells, while lower levels of Dpp reaching the prospective embryonic eye primordium may activate eya and so. This situation has parallels with the role of BMP signaling during eye placode specification in vertebrate embryos (Brugmann et al., 2004). The maintenance of eya and so in the subsequently developing eye lobe may be independent of Dpp. This situation would mirror the relationship between dpp and early retinal genes in the Drosophila eye disc. Both Hh and Dpp signaling are essential for activation but not maintenance of eya expression (Curtiss and Mlodzik, 2000). The function of dpp expression in the grasshopper PPN domain remains to be determined. Strategically, dpp would be positioned to repress eye selector antagonists. These, however, remain to be identified given the lack of differential exd expression in the grasshopper. In addition, Dpp might be involved in inducing new eya expressing cells in the anterior eye lobe once the morphogenetic furrow is moving through the eye lobe ectoderm.
th o
r's
pe
rs
primordium patterning in primitive insects comes from examination of Exd expression in the embryonic head of grasshopper (Dong and Friedrich, 2005a). Differential Exd expression is neither detectable prior nor subsequent to the initiation of eye primordium differentiation in this species. These data point against a role of hth and exd in embryonic visual system patterning of primitive insects (Dong and Friedrich, 2005a). Zen and tll act as eye fate antagonists in the Drosophila embryo. In primitive insects, zen is exclusively expressed in the peripheral extraembryonic membranes, first in the serosa and later in the amnion (Dearden et al., 2000). Thus, zen is not functioning as eye fate antagonist within the embryonic head neuroectoderm proper. Zen is coexpressed with dpp in the necklace cells, the precursors of the extra-embryonic serosa outlining the germband periphery (Dearden and Akam, 2001). This situation is compatible with a Drosophila inspired model, in which high levels of Dpp signaling activate zen expression to specify serosa over germband fate. In support of this model, knockdown of the zen-1 paralog in the primitive short germ embryo of Tribolium leads to the transformation of serosa cells into germband (van der Zee et al., 2005). This is associated with an extension of head patterning genes including orthodenticle (otd) (van der Zee et al., 2005). Although not related to head midline patterning as in Drosophila, this phenotype positions zen and high level Dpp as putative ancestral repressors of germband fate condition and, secondarily, eye primordium fate. tll has not yet been studied in non-holometabolous insects. However, tll is a conserved component of embryonic head development in vertebrates suggesting a likewise conserved role in primitive insects (Monaghan et al., 1995). In the embryonic head of Tribolium, tll expression extends over a large protocerebral domain that includes the precursor tissue of the optic lobe anlagen (Schroder et al., 2000). Very similar to the situation in the Drosophila embryo, Tribolium tll is not expressed in the larval eye anlage (Yang and Friedrich, unpublished). This leads to the prediction that the function of tll in specifying optic lobe over larval eye fate is conserved.
on
322
Signal transduction pathways
Au
The expression of wg, dpp and hh has been studied in detail in the embryonic head of hemimetabolous insects. The available data are largely consistent with the conclusion from eye specification network comparison in Drosophila, that these signaling pathways execute highly conserved instructions in the specification and differentiation of visual organ primordia. Dpp
Wg At first glance, the expression of dpp in the embryonic visual system of hemimetabolous insects is difficult to relate to its function in the Drosophila visual system (Friedrich and Benzer, 2000). In the grasshopper, dpp is expressed at low levels in small fields of the head lobes of the early germband
Key aspects of the expression of wg in the embryonic visual system of hemimetabolous insects correspond well to that in the late Drosophila eye-antennal disc. In grasshopper, cricket and milkweed bug, strong expression domains build up at the dorsal
M. Friedrich / Developmental Biology 299 (2006) 310–329
Hh
on
al
co
py
The expression of hh has been described in the embryonic head of cricket (Niwa et al., 2004). Early expression of hh is seen in each of the head lobes in stripe-like domains posterior to the expression of wg, thus marking the posterior border of the anterior procephalon or ocular segment (Liu et al., in press). Whether hh is expressed in the ectoderm of fully developed eye lobes prior to retinal differentiation awaits investigation. Strong expression, however, can be seen in the differentiating embryonic eye suggesting a conserved role of hh in driving differentiation (Miyawaki et al., 2004; Niwa et al., 2004). Consistent observations have been made in the developing visual system of Tribolium (Liu et al., in press). Also in this case, hh marks the posterior border of the ocular segment. The ocular segment expression domain of hh becomes situated in a tissue fold, which separates the antennal primordium from the head lobes and the visual anlage (Liu et al., in press). No hh expression is detectable in the visual anlage proper prior to differentiation of the larval eye primordium. Onset of hh expression occurs in the differentiating larval eye photoreceptor cells (Yang and Friedrich, unpublished observations). This is highly reminiscent of the expression of hh in photoreceptor cells close to the morphogenetic furrow in the differenting Drosophila retina. Thus while hh is unlikely to activate dpp prior to differentiation in the flour beetle embryo, its expression in the differentiating larval eye primordium is compatible with a conserved function in promoting neuronal specification.
Au
th o
r's
pe
rs
and ventral poles in front of the developing eye lobe ectoderm (Angelini and Kaufman, 2005; Friedrich and Benzer, 2000; Niwa et al., 2000). Similar and hence ancestral polar expression domains characterize the third instar Drosophila eye-antennal disc. Neuroectodermal expression of wg in the ocular segment of the embryo, on the other hand, has been reduced to a single domain anterior to the larval eye anlage (Liu et al., in press; Schmidt-Ott and Technau, 1992). These data would suggest a stronger correspondence of Drosophila adult compound eye primordium specification and embryonic patterning of the visual system in primitive insects. However, as mentioned above, data from Tribolium provide evidence that the situation in the Drosophila embryo is derived. In Tribolium, wg is expressed in polar domains in front of both, the embryonic larval eye, and the postembryonic eye placode (Liu et al., in press). Thus, the ancestral polar wg expression domains are already initiated during embryogenesis in eucephalic holometabolous species. It follows that the neuroectoderm restricted expression of wg in the embryonic ocular segment of Drosophila is the result of evolutionary reduction (Liu et al., in press). The similarity of wg expression in the embryonic head of grasshopper and the Drosophila eye-antennal disc suggests that the function of Wg in repressing eye determination and differentiation is conserved (Friedrich and Benzer, 2000). In line with a repressive effect on early retinal genes, the expression domains of wg appear largely exclusive of that of eya and so in the grasshopper eye lobes (Dong and Friedrich, 2005a). Furthermore, activating Wg signaling in cultured grasshopper embryonic eye primordia with LiCl blocks morphogenetic furrow progression (Dong and Friedrich, 2005a). The same manipulation triggers elevated cell division in the undifferentiated eye lobe ectoderm anterior of the furrow (Dong and Friedrich, 2005a). These data support the hypothesis that repression of eye differentiation combined with activation of precursor tissue proliferation by Wg is an ancestral element of insect eye primordium patterning (Fig. 3c) (Dong and Friedrich, 2005a). Embryonic knockdown experiments targeting components of the Wg signaling pathway have been carried out in the milkweed bug and cricket (Angelini and Kaufman, 2005; Miyawaki et al., 2004). Reduced eye phenotypes have been reported for wg depleted embryos in Oncopeltus (Angelini and Kaufman, 2005). This phenotype resembles the reduced eye phenotype in Drosophila, which results from early suppression of Wg signaling and has been interpreted to reflect the role of Wg in eye primordium proliferation (Kaphingst and Kunes, 1994; Ma and Moses, 1995). However, when the Wg signal mediating transcription cofactor pangolin (pan) was targeted by RNAi in Oncopeltus, dorsal expansion of eye field was observed indicative of a repressive effect during normal development (Angelini and Kaufman, 2005). Opposing effects have also been obtained from manipulating different Wg signaling pathway components in the Drosophila eye disc reflecting involvement in both primordium growth and repression of primordium differentiation (Baonza and Freeman, 2002; Hazelett et al., 1998; Lee and Treisman, 2001; Singh et al., 2002).
323
Evolving postembryonic compound eye determination in Drosophila: a proposal The selector gene arsenal likely deployed during embryonic compound eye specification in primitive insects exhibits unique similarities to the Drosophila larval eye specification gene network. Tll and zen are specifically involved in delimiting the embryonic eye primordium dimensions in Drosophila as well as directly developing species (Fig. 3) (Daniel et al., 1999). The differential involvement of these genes reflects different tissue determination decisions during Drosophila larval and adult eye development. During larval eye development, extra-embryonic tissues, optic lobe, eye disc and the Bolwig organ primordia need to be defined. Postembryonic compound eye primordium specification, on the other hand, requires separation from other head ectoderm compartments, but not neuronal tissues. Even more remarkable is the restriction of tissue growth maintenance by hth and tsh to the developing eye-antennal imaginal disc. The currently available evidence suggests that neither the Drosophila embryonic visual anlage, nor the embryonic compound eye primordia of hemimetabolous insects employ patterning by tsh and hth. The lack of a growth stimulating transcription factor complex in larval eye primordium patterning is not surprising considering the extreme size reduction of the Drosophila larval visual system. However, the shared lack of hth and tsh patterning function in the embryonic head of directly developing insects implies that this constel-
M. Friedrich / Developmental Biology 299 (2006) 310–329
rs
on
al
co
py
324
pe
Fig. 4. Hypothesized molecular regulatory changes in the eye primordium of hemimetabolous insects during the transition from embryonic to postembryonic eye development and its relation to the molecular regulation of eye-antennal disc patterning in Drosophila. Expression domains of Schistocerca ato and tsh, as well as all postembryonic Schistocerca expression domains are hypothetical taking into account evidence from postembryonic eye determination in Drosophila and embryonic expression patterns in Schistocerca. The embryonic Schistocerca Pax-6 expression domain is based on preliminary results (Dong and Friedrich, unpublished). Note the possible similarity between the developmental organization of the proliferation zone in the postembryonic grasshopper eye (pro), the early Drosophila eyeantennal disc, and the proliferative domain II in the differentiating Drosophila eye-antennal disc. Dif = differentiation zone, mf = morphogenetic furrow, PPN = preproneural domain, I = domain I, II = domain II, ant = antenna disc field.
Au
th o
r's
lation is not specific for species with reduced juvenile head morphologies, but applies to insect embryonic head patterning in general. How the differential expression of optix fits into this picture awaits lack of function analyses in Drosophila and other insect species. Overall, the available data indicate a higher correspondence of gene activities involved in Drosophila Bolwig organ specification and embryonic compound eye formation in primitive insects. This supports the model that differences between the Drosophila larval and adult compound eye determination gene networks reflect ancestral differences in the molecular control of embryonic and postembryonic eye primordium development. Consistent with this possibility is the fact that the continuity of compound eye development in nonholometabolous species is associated with a substantial reorganization of retina morphogenesis (Fig. 4). The embryonic compound eye primordium emerges via separation of optic lobe from retina precursor cells in the visual anlagen field of the head neuroectoderm. Starting within a large field of retinal anlagen tissue, the embryonic phase of compound eye development involves progressive, morphogenetic furrow-driven differentiation of compound eye retina. With beginning of the postembryonic phase, the embryonic neuroectoderm-derived anlagen cells have been consumed and replaced by the stem cell-like
proliferation zone in the front of the nymphal eye (Anderson, 1978). The postembryonic phase is characterized by a gradual differentiation of cells which are continuously produced in the proliferation zone. This reorganization of retinal development may be associated with differences in the molecular constitution of the retinal precursor cells (Fig. 4). Tentative evidence for reorganization at the molecular level may be seen in aspects of wg expression during embryonic eye lobe development in grasshopper (Fig. 4) (Dong and Friedrich, 2005a). Wg is initially expressed in lateral domains of a fold separating the retinal primordium from adjacent head neuroectoderm, and thus outside of the grasshopper eye lobe. About midway through embryogenesis, the wg expression domains begin to change their relative position and gradually move into the eye field. Eventually, wg is expressed in a narrow, peripheral-most rim of cells outlining the anterior eye lobe ectoderm margin (Fig. 4) (Dong and Friedrich, 2005a). Interestingly, Wnt signaling is involved in retinal stem cell maintenance in vertebrates (Kubo et al., 2003). In the chicken ciliary margin, Wnt signaling controls retinal precursor cell levels by repressing differentiation and activating cell proliferation (Kubo et al., 2005). These mechanisms are of striking resemblance to the effect of Wg on eye development in the Drosophila eye disc or in the grasshopper eye lobe. It is
M. Friedrich / Developmental Biology 299 (2006) 310–329
on
al
co
py
however, indicates distribution of Wg protein in the entire eyeantennal disc (Royet and Finkelstein, 1997). The overlap of eye fate promoting and antagonizing gene activities suggests that the early eye-antennal disc constitutes a field of developmentally equipotent cells. This transcriptional state may be related to cells in the retinal growth zone of the grasshopper and other primitive insects. One tempting scenario is that the evolution of the Drosophila eye-antennal disc started from an ancestral postembryonic eye primordium, which transformed into the secondary morphogenetic field of the eye-antennal disc. The spatially enlarged secondary morphogenetic field facilitated the heterochronic initiation of progressive retinal differentiation in the larva (Fig. 4). In this view, the proliferation zone in the nymphal eye of hemimetabolous insects may be equivalent to the proliferating domain II in the Drosophila eye-antennal imaginal disc, which receives Wg signaling input and expresses ey, hth and tsh (Fig. 3). Transcription of the latter two genes, proposed to build a cell proliferation stimulating complex with Ey (Bessa et al., 2002), may be activated in the proliferation zone. This activation may occur by increased Wg signaling levels in the anterior eye lobe margin or by addition of external signaling factors. This scenario provides a specific explanatory model for the evolution of the Drosophila compound eye primordium. It remains to be further explored which evolutionary pathways lead to the multiprimordium character of the eye antennal disc.
Au
th o
r's
pe
rs
therefore tempting to speculate that the transcriptional status of the grasshopper proliferation zone involves Wg. It is also possible that the integration of wg into the eye lobe is related to evolutionary conservation of a function in eye margin patterning. In Drosophila, wg is expressed along the circumference of the pupal eye (Tomlinson, 2003). This expression is essential for patterning many aspects of the compound eye margin including the elimination of irregular ommatidia and suppression of bristle development (Lin et al., 2004; Tomlinson, 2003). The above considerations suggest that the Drosophila eye disc is evolutionarily related to the postembryonic growth zone-like eye primordium of directly developing insects. This relationship is in line with the transient arrest theory of the evolution of biphasic visual system development. Nonetheless, it is hardly possible to consider the Drosophila compound eye primordium a reinitiated growth zone. The eye antennal disc derives cellular material from different embryonic head segments and provides cell resources for a large variety of different cell compartments in the adult head besides the eye. The question of how this multi-organ precursor cell population evolved remains. According to the transient arrest model, the adult compound eye of holometabolous insects is the product of reinitiated retinal differentiation. This situation appears to still exist in scorpion flies (Fig. 2). Also the reinitiation of polar wg expression domains in front of the adult eye placodes in the flower beetle is compatible with the transient arrest scenario (Friedrich and Benzer, 2000; Liu et al., in press). The de novo development of all major head cuticle compartments from larval body plan independent primordia in Drosophila, however, is a fundamentally different situation. The Drosophila compound eye primordium may either represent the duplication of an embryonic eye primordium, or the reinitiation of a highly derived form of a postembryogenesis specific eye primordium. The former view is supported by the initiation of progressive retinal differentiation in the eye disc, which takes place in the embryonic but not postembryonic eye of non-homolometabolous insects. For the latter view speaks the distinct transcription factor make-up of the early eyeantennal disc. In this context, it is further instructive to consider the gene expression dynamics in the Drosophila eye-antennal imaginal disc. The first larval instar eye-antennal disc is characterized by uniform expression of selector and signaling factor genes (Fig. 4). In line with their top positions in the compound eye specification gene network, ey and toy are the first core eye selector genes, which can be detected at this stage (Czerny et al., 1999; Quiring et al., 1994; Singh et al., 2002). Their expression is supplemented with that of eye fate antagonists hth and exd which are likewise uniformly expressed (Pichaud and Casares, 2000; Singh et al., 2002). The overlapping expression of eye fate promoting and antagonistic selector genes is mirrored at the signaling molecule level. Dpp and Wg are expressed throughout the anteroposterior axis of the early disc (Cho et al., 2000; Pichaud and Casares, 2000; Royet and Finkelstein, 1997). Reporter gene expression suggests that dpp expression is located in peripodial cells of the ventral disc, while that of wg is predominantly dorsal (Cho et al., 2000; Pichaud and Casares, 2000). Immunohistochemical detection,
325
Perspectives Three important lines of future research emerge from the current understanding of the evolution of insect eye development: (I) The proposed homology between the Drosophila eyeantennal imaginal disc and the growth zone of the nymphal eye in primitive insects has important conceptual implications. It is therefore unfortunate that no information is available yet in regards to the molecular control of the postembryonic retina differentiation in nonholometabolous insects. The feasibility of gene knockdown experiments in juvenile instars of hemimetabolous species will greatly enhance the study of this important issue (Dong and Friedrich, 2005b; Mito et al., 2005). Investigating the ancestral differences in the control of embryonic and postembryonic insect eye primordium patterning will not only be of essential for fully understanding the molecular logic of Drosophila eye development. It will also generate the necessary reference for comparing the molecular regulation of postembryonic retinal differentiation of the vertebrate retina (Mito et al., 2005; Perron and Harris, 2000). (II) Similarities in selector gene expression profiles may be indicative of homology between widely diverged structures, such as the Drosophila eye-antennal disc and the nymphal growth zone. However, they still run short of representing satisfactory evidence of the implied homology relationship. Secondly, the evolutionary course of this
M. Friedrich / Developmental Biology 299 (2006) 310–329
al
co
py
ticle protein is spatially regulated throughout development in Drosophila. Development 124, 741–747. Baker, N.E., 2001. Master regulatory genes; telling them what to do. BioEssays 23, 763–766. Baonza, A., Freeman, M., 2002. Control of Drosophila eye specification by Wingless signalling. Development 129, 5313–5322. Bate, C.M., 1978. Development of sensory systems in Arthropods. In: Jacobson, M. (Ed.), Handbook of sensory physiology, vol. 9. Springer Verlag, Heidelberg, NY, pp. 1–53. Bessa, J., Casares, F., 2005. Restricted teashirt expression confers eye-specific responsiveness to Dpp and Wg signals during eye specification in Drosophila. Development 132, 5011–5020. Bessa, J., Gebelein, B., Pichaud, F., Casares, F., Mann, R.S., 2002. Combinatorial control of Drosophila eye development by eyeless, homothorax, and teashirt. Genes Dev. 16, 2415–2427. Bodenstein, D., 1953. Postembryonic development. In: Roeder, K.D. (Ed.), Insect Physiology. Wiley, New York, pp. 275–367. Bolwig, N., 1946. Senses and sense organs of the anterior end of the house fly larvae. Vidensk. Medd. Dan. Naturhist. Foren. 109, 81–217. Bonini, N.M., Leiserson, W.M., Benzer, S., 1993. The eyes absent gene: genetic control of cell survival and differentiation in the developing Drosophila eye. Cell 72, 379–395. Bonini, N.M., Bui, Q.T., Gray-Board, G.L., Warrick, J.M., 1997. The Drosophila eyes absent gene directs ectopic eye formation in a pathway conserved between flies and vertebrates. Development 124, 4819–4826. Briscoe, A.D., White, R.H., 2005. Adult stemmata of the butterfly Vanessa cardui express UV and green opsin mRNAs. Cell Tissue Res. 319, 175–179. Brown, S.J., Denell, R.E., Beeman, R.W., 2003. Beetling around the genome. Genet. Res. 82, 155–161. Brugmann, S.A., Pandur, P.D., Kenyon, K.L., Pignoni, F., Moody, S.A., 2004. Six1 promotes a placodal fate within the lateral neurogenic ectoderm by functioning as both a transcriptional activator and repressor. Development 131, 5871–5881. Burke, R., Basler, K., 1996. Hedgehog-dependent patterning in the Drosophila eye can occur in the absence of Dpp signaling. Dev. Biol. 179, 360–368. Cadigan, K.M., Jou, A.D., Nusse, R., 2002. Wingless blocks bristle formation and morphogenetic furrow progression in the eye through repression of Daughterless. Development 129, 3393–3402. Champlin, D.T., Truman, J.W., 1998. Ecdysteroids govern two phases of eye development during metamorphosis of the moth, Manduca sexta. Development 125, 2009–2018. Chang, T., Mazotta, J., Dumstrei, K., Dumitrescu, A., Hartenstein, V., 2001. Dpp and Hh signaling in the Drosophila embryonic eye field. Development 128, 4691–4704. Chanut, F., Heberlein, U., 1997. Role of decapentaplegic in initiation and progression of the morphogenetic furrow in the developing Drosophila retina. Development 124, 559–567. Chen, R., Amoui, M., Zhang, Z., Mardon, G., 1997. Dachshund and Eyes absent proteins form a complex and function synergistically to induce ectopic eye development in Drosophila. Cell 91, 893–903. Cheyette, B.N., Green, P.J., Martin, K., Garren, H., Hartenstein, V., Zipursky, S.L., 1994. The Drosophila sine oculis locus encodes a homeodomaincontaining protein required for the development of the entire visual system. Neuron 12, 977–996. Cho, K.O., Chern, J., Izaddoost, S., Choi, K.W., 2000. Novel signaling from the peripodial membrane is essential for eye disc patterning in Drosophila. Cell 103, 331–342. Curtiss, J., Mlodzik, M., 2000. Morphogenetic furrow initiation and progression during eye development in Drosophila: the roles of decapentaplegic, hedgehog and eyes absent. Development 127, 1325–1336. Czerny, T., Halder, G., Kloter, U., Souabni, A., Gehring, W.J., Busslinger, M., 1999. Twin of eyeless, a second Pax-6 gene of Drosophila, acts upstream of eyeless in the control of eye development. Mol. Cell 3, 297–307. Daniel, A., Dumstrei, K., Lengyel, J.A., Hartenstein, V., 1999. The control of cell fate in the embryonic visual system by atonal, tailless and EGFR signaling. Development 126, 2945–2954. Davis, R.J., Shen, W., Sandler, Y.I., Amoui, M., Purcell, P., Maas, R., Ou, C.N., Vogel, H., Beaudet, A.L., Mardon, G., 2001. Dach1 mutant mice bear no
pe
rs
extreme structural transformation remains to be elucidated. This opportunity exists in the Diptera. Extant species in higher flies still harbor representative intermediate stages of larval head reduction (Melzer and Paulus, 1989). It will be very interesting to retrace the evolutionary origin of the eye-antennal disc by comparative study of head imaginal disc development in cycorrhaphan flies. (III) Although the Drosophila eye-antennal disc poses fascinating questions regarding the evolution of development, it has also become clear that is not the best system for the reconstruction of early events in the evolution of biphasic visual system development in primitive insects. For this, it will be necessary to work with lesser-derived species in which larval and adult body plan development is not entirely dissociated. Studying the visual system of scorpion flies would be important, considering the ancestral organization of the larval eye. In the short run, however, Tribolium appears exceptionally well positioned, given its ancestral organization of visual system development and the availability of genomic and molecular genetic resources (Brown et al., 2003; Friedrich and Benzer, 2000). An obvious test of the developmental arrest model is to investigate if visual system development in lesser-derived holometabolous species is associated with an intermediate pausing of eye selector gene expression. The available data on dpp and wg expression in Tribolium are consistent with this prediction, but need to be extended to selector genes (Friedrich and Benzer, 2000).
on
326
Acknowledgments
Au
References
th o
r's
Thanks are due to former and present lab members Ying Dong, Xiaoyun Yang, and Dilip Gill for reading the manuscript, Ivanna Yavorenko for enduring proofreading assistance, two anonymous reviewers for helpful suggestions on the initial draft of the manuscript, and the Klingler lab for providing a stimulating atmosphere during the final phase of manuscript preparation. This work was supported by grant DBI-0091926 from the National Science Foundation and a Career Development Chair Award by Wayne State University.
Anderson, H., 1978. Postembryonic development of the visual system of the locust, Schistocerca gregaria. I. Pattern of growth and developmental interactions in the retina and optic lobe. J. Embryol. Exp. Morphol. 45, 55–83. Ando, H., Suzuki, N., 1977. On the embryonic development of the larval eyes of the scorpion fly, Panorpa pryeri MacLachlan (Mecoptera, Panorpidae). Proc. Jpn. Soc. Syst. 81–84. Angelini, D.R., Kaufman, T.C., 2004. Functional analyses in the hemipteran Oncopeltus fasciatus reveal conserved and derived aspects of appendage patterning in insects. Dev. Biol. 271, 306–321. Angelini, D.R., Kaufman, T.C., 2005. Functional analyses in the milkweed bug Oncopeltus fasciatus (Hemiptera) support a role for Wnt signaling in body segmentation but not appendage development. Dev. Biol. 283 (2), 409–423. Aspland, S.E., White, R.A., 1997. Nucleocytoplasmic localisation of extraden-
M. Friedrich / Developmental Biology 299 (2006) 310–329
on
al
co
py
Hagberg, M., 1986. Ultrastructure and central projections of extraocular photoreceptors in caddiesflies (Insecta, Trichoptera). Cell Tissue Res. 245, 643–648. Halder, G., Callaerts, P., Gehring, W.J., 1995. Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila. Science 267, 1788–1792. Halder, G., Callaerts, P., Flister, S., Walldorf, U., Kloter, U., Gehring, W.J., 1998. Eyeless initiates the expression of both sine oculis and eyes absent during Drosophila compound eye development. Development 125, 2181–2191. Hay, B.A., Wolff, T., Rubin, G.M., 1994. Expression of baculovirus P35 prevents cell death in Drosophila. Development 120, 2121–2129. Hayashi, T., Saigo, K., 2001. Diversification of cell types in the Drosophila eye by differential expression of prepattern genes. Mech. Dev. 108, 13–27. Haynie, J.L., Bryant, P.J., 1986. Development of the eye-antenna imaginal disc and morphogenesis of the adult head in Drosophila melanogaster. J. Exp. Zool. 237, 293–308. Hazelett, D.J., Bourouis, M., Walldorf, U., Treisman, J.E., 1998. Decapentaplegic and wingless are regulated by eyes absent and eyegone and interact to direct the pattern of retinal differentiation in the eye disc. Development 125, 3741–3751. Heanue, T.A., Reshef, R., Davis, R.J., Mardon, G., Oliver, G., Tomarev, S., Lassar, A.B., Tabin, C.J., 1999. Synergistic regulation of vertebrate muscle development by Dach2, Eya2, and Six1, homologs of genes required for Drosophila eye formation. Genes Dev. 13, 3231–3243. Heberlein, U., Wolff, T., Rubin, G.M., 1993. The TGF beta homolog dpp and the segment polarity gene hedgehog are required for propagation of a morphogenetic wave in the Drosophila retina. Cell 75, 913–926. Helfrich-Forster, C., Edwards, T., Yasuyama, K., Wisotzki, B., Schneuwly, S., Stanewsky, R., Meinertzhagen, I.A., Hofbauer, A., 2002. The extraretinal eyelet of Drosophila: development, ultrastructure, and putative circadian function. J. Neurosci. 22, 9255–9266. Heming, B.S., 1982. Structure and development of the larval visual system in embryos of Lytta viridana Leconte (Coleoptera, Meloidae). J. Morphol. 172, 23–43. Herke, S.W., Serio, N.V., Rogers, B.T., 2005. Functional analyses of tiptop and Antennapedia in the embryonic development of Oncopeltus fasciatus suggests an evolutionary pathway from ground state to insect legs. Development 132, 27–34. Ichikawa, T., 1991. Brain photoreceptors in the pupal and adult butterfly: fate of the larval ocelli. Zool. Sci. 8, 471–476. Inoue, Y., Miyawaki, K., Terasawa, T., Matsushima, K., Shinmyo, Y., Niwa, N., Mito, T., Ohuchi, H., Noji, S., 2004. Expression patterns of dachshund during head development of Gryllus bimaculatus (cricket). Gene Expr. Patterns 4, 725–731. Kaphingst, K., Kunes, S., 1994. Pattern formation in the visual centers of the Drosophila brain: wingless acts via decapentaplegic to specify the dorsoventral axis. Cell 78, 437–448. Kenyon, K.L., Ranade, S.S., Curtiss, J., Mlodzik, M., Pignoni, F., 2003. Coordinating proliferation and tissue specification to promote regional identity in the Drosophila head. Dev. Cell 5, 403–414. Kubo, F., Takeichi, M., Nakagawa, S., 2003. Wnt2b controls retinal cell differentiation at the ciliary marginal zone. Development 130, 587–598. Kubo, F., Takeichi, M., Nakagawa, S., 2005. Wnt2b inhibits differentiation of retinal progenitor cells in the absence of Notch activity by downregulating the expression of proneural genes. Development 132, 2759–2770. Kumar, J.P., Moses, K., 2001a. EGF receptor and Notch signaling act upstream of Eyeless/Pax6 to control eye specification. Cell 104, 687–697. Kumar, J.P., Moses, K., 2001b. Expression of evolutionarily conserved eye specification genes during Drosophila embryogenesis. Dev. Genes Evol. 211, 406–414. Kurant, E., Pai, C.Y., Sharf, R., Halachmi, N., Sun, Y.H., Salzberg, A., 1998. Dorsotonals/homothorax, the Drosophila homologue of meis1, interacts with extradenticle in patterning of the embryonic PNS. Development 125, 1037–1048. Laugier, E., Yang, Z., Fasano, L., Kerridge, S., Vola, C., 2005. A critical role of teashirt for patterning the ventral epidermis is masked by ectopic expression of tiptop, a paralog of teashirt in Drosophila. Dev. Biol. 283, 446–458.
Au
th o
r's
pe
rs
gross abnormalities in eye, limb, and brain development and exhibit postnatal lethality. Mol. Cell. Biol. 21, 1484–1490. Dearden, P.K., Akam, M., 2001. Early embryo patterning in the grasshopper, Schistocerca gregaria: wingless, decapentaplegic and caudal expression. Development 128, 3435–3444. Dearden, P., Grbic, M., Falciani, F., Akam, M., 2000. Maternal expression and early zygotic regulation of the Hox3/zen gene in the grasshopper Schistocerca gregaria. Evol. Dev. 2, 261–270. Desplan, C., 1997. Eye development: governed by a dictator or a junta? Cell 91, 861–864. Dominguez, M., 1999. Dual role for Hedgehog in the regulation of the proneural gene atonal during ommatidia development. Development 126, 2345–2353. Dominguez, M., Casares, F., 2005. Organ specification-growth control connection: new in-sights from the Drosophila eye-antennal disc. Dev. Dyn. 232, 673–684. Dominguez, M., Hafen, E., 1997. Hedgehog directly controls initiation and propagation of retinal differentiation in the Drosophila eye. Genes Dev. 11, 3254–3264. Dong, Y., Friedrich, M., 2005a. Comparative analysis of Wg patterning in the embryonic grasshopper eye. Dev. Genes Evol. 215, 177–197. Dong, Y., Friedrich, M., 2005b. Nymphal RNAi: systemic RNAi mediated gene knockdown in juvenile grasshopper. BMC Biotechnol. 5, 25. Dong, Y., Dinan, L., Friedrich, M., 2003. The effect of manipulating ecdysteroid signaling on embryonic eye development in the locust Schistocerca americana. Dev. Genes Evol. 213, 587–600. Donner, A.L., Maas, R.L., 2004. Conservation and non-conservation of genetic pathways in eye specification. Int. J. Dev. Biol. 48, 743–753. Egelhaaf, A., 1988. Evidence for the priming role of the central retinula cell in ommatidium differentiation of Ephestia kuehniella. Roux's Arch. Dev. Biol. 197, 184–189. Fasano, L., Roder, L., Core, N., Alexandre, E., Vola, C., Jacq, B., Kerridge, S., 1991. The gene teashirt is required for the development of Drosophila embryonic trunk segments and encodes a protein with widely spaced zinc finger motifs. Cell 64, 63–79. Ferrier, D.E., Akam, M., 1996. Organization of the Hox gene cluster in the grasshopper, Schistocerca gregaria. Proc. Natl. Acad. Sci. U. S. A. 93, 13024–13029. Fleissner, G., Fleissner, G., Frisch, B., 1993. A new type of putative non-visual photoreceptors in the optic lobe of beetles. Cell Tissue Res. 273, 435–445. Flores, G.V., Daga, A., Kalhor, H.R., Banerjee, U., 1998. Lozenge is expressed in pluripotent precursor cells and patterns multiple cell types in the Drosophila eye through the control of cell-specific transcription factors. Development 125, 3681–3687. Friedrich, M., 2003. Evolution of insect eye development: first insights from fruit fly, grasshopper and flour beetle. Integr. Comp. Biol. 43, 508–521. Friedrich, M., in press. Ancient mechanisms of visual sense organ development based on comparison of the gene networks regulating larval eye, ocellus and compound eye specification in Drosophila. Arth. Struc. and Dev. Friedrich, M., Dong, Y., Jackowska, M., in press. Insect interordinal relationships: insights from the visual system. Entomologische Abhandlungen. Friedrich, M., Benzer, S., 2000. Divergent decapentaplegic expression patterns in compound eye development and the evolution of insect metamorphosis. J. Exp. Zool. (Mol. Dev. Evol.) 288, 39–55. Friedrich, M., Rambold, I., Melzer, R.R., 1996. The early stages of ommatidial development in the flour beetle Tribolium castaneum (Coleoptera, Tenebrionidae). Dev. Genes Evol. 206, 136–146. Friedrichs, H.F., 1931. Beitrage zur Morphologie und Physiologie der Sehorgane der Cicindeliden (Col.). Z. Morphol. Okol. 1–172. Gehring, W.J., 2002. The genetic control of eye development and its implications for the evolution of the various eye-types. Int. J. Dev. Biol. 46, 65–73. Gilbert, C., 1994. Form and function of stemmata in larvae of holometabolous insects. Annu. Rev. Entomol. 39, 323–349. Green, P., Hartenstein, A.Y., Hartenstein, V., 1993. The embryonic development of the Drosophila visual-system. Cell Tissue Res. 273, 583–598. Greenwood, S., Struhl, G., 1999. Progression of the morphogenetic furrow in the Drosophila eye: the roles of Hedgehog, Decapentaplegic and the Raf pathway. Development 126, 5795–5808.
327
M. Friedrich / Developmental Biology 299 (2006) 310–329
al
co
py
Pappu, K.S., Mardon, G., 2004. Genetic control of retinal specification and determination in Drosophila. Int. J. Dev. Biol. 48, 913–924. Pappu, K.S., Chen, R., Middlebrooks, B.W., Woo, C., Heberlein, U., Mardon, G., 2003. Mechanism of hedgehog signaling during Drosophila eye development. Development 130, 3053–3062. Pappu, K.S., Ostrin, E.J., Middlebrooks, B.W., Sili, B.T., Chen, R., Atkins, M.R., Gibbs, R., Mardon, G., 2005. Dual regulation and redundant function of two eye-specific enhancers of the Drosophila retinal determination gene dachshund. Development 132, 2895–2905. Paulus, H.F., 1979. Eye structure and the monophyly of the Arthropoda. In: Gupta, A.P. (Ed.), Arthropod Phylogeny. Van Nostand Reinhold Company, New York, pp. 299–371. Paulus, H., 1986. Evolutionswege zum Larvalauge der Insekten - ein Modell für die Entstehung und die Ableitung der ozellären Lateralaugen der Myriapoda von Fazettenaugen. Zool. Jahrb. 353–371. Paulus, H.F., 1989. Das Homologisieren in der Feinstrukturforschung: Das Bolwig-Organ der hoeheren Dipteren und seine Homologisierung mit Stemmata und Ommatidien eines urspruenglichen Facettenauges der Mandibulata. Zool. Beitr. N.F. 32, 437–478. Perron, M., Harris, W.A., 2000. Retinal stem cells in vertebrates. BioEssays 22, 685–688. Pichaud, F., Casares, F., 2000. Homothorax and iroquois-C genes are required for the establishment of territories within the developing eye disc. Mech. Dev. 96, 15–25. Pichaud, F., Deplan, C., 2001. A new visualization approach for identifying mutations that affect differentiation and organization of the Drosophila ommatidia. Development 128, 815–826. Pignoni, F., Zipursky, S.L., 1997. Induction of Drosophila eye development by decapentaplegic. Development 124, 271–278. Pignoni, F., Baldarelli, R.M., Steingrimsson, E., Diaz, R.J., Patapoutian, A., Merriam, J.R., Lengyel, J.A., 1990. The Drosophila gene tailless is expressed at the embryonic termini and is a member of the steroid receptor superfamily. Cell 62, 151–163. Pignoni, F., Hu, B., Zavitz, K.H., Xiao, J., Garrity, P.A., Zipursky, S.L., 1997. The eye-specification proteins So and Eya form a complex and regulate multiple steps in Drosophila eye development. Cell 91, 881–891. Pollock, J.A., Benzer, S., 1988. Transcript localization of four opsin genes in the three visual organs of Drosophila; RH2 is ocellus specific. Nature 333, 779–782. Postlethwait, J.H., Schneiderman, H.A., 1971. A clonal analysis of development in Drosophila melanogaster: morphogenesis, determination and growth in the wild type antenna. Dev. Biol. 24, 477–519. Prpic, N.M., 2005. Duplicated Pax6 genes in Glomeris marginata (Myriapoda: Diplopoda), an arthropod with simple lateral eyes. Zoology 108, 47–53. Punzo, C., Seimiya, M., Flister, S., Gehring, W.J., Plaza, S., 2002. Differential interactions of eyeless and twin of eyeless with the sine oculis enhancer. Development 129, 625–634. Quiring, R., Walldorf, U., Kloter, U., Gehring, W.J., 1994. Homology of the eyeless gene of Drosophila to the Small eye gene in mice and Aniridia in humans. Science 265, 785–789. Rayapureddi, J.P., Kattamuri, C., Steinmetz, B.D., Frankfort, B.J., Ostrin, E.J., Mardon, G., Hegde, R.S., 2003. Eyes absent represents a class of protein tyrosine phosphatases. Nature 426, 295–298. Rieckhof, G.E., Casares, F., Ryoo, H.D., Abu-Shaar, M., Mann, R.S., 1997. Nuclear translocation of Extradenticle requires Homothorax, which encodes an Extradenticle-related homeodomain protein. Cell 91, 171–183. Roonwal, M.L., 1936. Studies on the embryology of the African migratory locust, Locusta migratoria migratorioides Reiche and Frm. (Orthoptera, Acrididae) II-Organogeny. Philos. Trans. R. Soc. Lond., B 227, 175–244. Royet, J., Finkelstein, R., 1997. Establishing primordia in the Drosophila eyeantennal imaginal disc—The roles of decapentaplegic, wingless and hedgehog. Development 124, 4793–4800. Rudolph, K.M., Liaw, G.J., Daniel, A., Green, P., Courey, A.J., Hartenstein, V., Lengyel, J.A., 1997. Complex regulatory region mediating tailless expression in early embryonic patterning and brain development. Development 124, 4297–4308. Rushlow, C., Doyle, H., Hoey, T., Levine, M., 1987. Molecular characterization
Au
th o
r's
pe
rs
Lee, J.D., Treisman, J.E., 2001. The role of Wingless signaling in establishing the anteroposterior and dorsoventral axes of the eye disc. Development 128, 1519–1529. Lin, H.V., Rogulja, A., Cadigan, K.M., 2004. Wingless eliminates ommatidia from the edge of the developing eye through activation of apoptosis. Development 131, 2409–2418. Liu, Z., Friedrich, M., 2004. The Tribolium homologue of glass and the evolution of insect larval eyes. Dev. Biol. 269, 36–54. Liu, Z., Yang, X., Dong, Y., and Friedrich, M. Tracking down the “head blob”: comparative analysis of wingless expression in the developing insect procephalon reveals progressive reduction of embryonic visual system patterning in higher insects. Arthropod Structure and Development, in press. Ma, C., Moses, K., 1995. Wingless and patched are negative regulators of the morphogenetic furrow and can affect tissue polarity in the developing Drosophila compound eye. Development 121, 2279–2289. Malpel, S., Klarsfeld, A., Rouyer, F., 2002. Larval optic nerve and adult extraretinal photoreceptors sequentially associate with clock neurons during Drosophila brain development. Development 129, 1443–1453. Mardon, G., Solomon, N.M., Rubin, G.M., 1994. Dachshund encodes a nuclear protein required for normal eye and leg development in Drosophila. Development 120, 3473–3486. Marshall, W.S., 1928. The development of the compound eye of the confused flour beetle, Tribolium confusum Jaqu. Trans. Wis. Acad. Sci. Arts Lett. 23, 611–630. Masucci, J.D., Miltenberger, R.J., Hoffmann, F.M., 1990. Pattern-specific expression of the Drosophila decapentaplegic gene in imaginal disks is regulated by 3′ cis-regulatory elements. Genes Dev. 4, 2011–2023. Mazzoni, E.O., Desplan, C., Blau, J., 2005. Circadian pacemaker neurons transmit and modulate visual information to control a rapid behavioral response. Neuron 45, 293–300. Meinertzhagen, I.A., 1973. Development of compound eye and optic lobe in insects. In: Young, D. (Ed.), Developmental Neurobiology of Arthropods. Cambridge Univ. Press, Cambridge, pp. 51–104. Melzer, R.R., Paulus, H.F., 1989. Evolutionswege zum Larvalauge der InsektenDie Stemmata der höheren Dipteren und ihre Abwandlung zum BolwigOrgan. Z. Zoolog. Syst. Evol.Forsch. 27, 200–245. Mito, T., Sarashina, I., Zhang, H., Iwahashi, A., Okamoto, H., Miyawaki, K., Shinmyo, Y., Ohuchi, H., Noji, S., 2005. Non-canonical functions of hunchback in segment patterning of the intermediate germ cricket Gryllus bimaculatus. Development 132, 2069–2079. Miyawaki, K., Mito, T., Sarashina, I., Zhang, H., Shinmyo, Y., Ohuchi, H., Noji, S., 2004. Involvement of Wingless/Armadillo signaling in the posterior sequential segmentation in the cricket, Gryllus bimaculatus (Orthoptera), as revealed by RNAi analysis. Mech. Dev. 121, 119–130. Monaghan, A.P., Grau, E., Bock, D., Schutz, G., 1995. The mouse homolog of the orphan nuclear receptor tailless is expressed in the developing forebrain. Development 121, 839–853. Monsma, S.A., Booker, R., 1996. Genesis of the adult retina and outer optic lobes of the moth, Manduca sexta. I. patterns of proliferation and cell death. J. Comp. Neurol. 367, 10–20. Niimi, T., Seimiya, M., Kloter, U., Flister, S., Gehring, W.J., 1999. Direct regulatory interaction of the Eyeless protein with an eye-specific enhancer in the sine oculis gene during eye induction in Drosophila. Development 126, 2253–2260. Niwa, N., Inoue, Y., Nozawa, A., Saito, M., Misumi, Y., Ohuchi, H., Yoshioka, H., Noji, S., 2000. Correlation of diversity of leg morphology in Gryllus bimaculatus (cricket) with divergence in dpp expression pattern during leg development. Development 127, 4373–4381. Niwa, N., Hiromi, Y., Okabe, M., 2004. A conserved developmental program for sensory organ formation in Drosophila melanogaster. Nat. Genet. 36, 293–297. Nowel, M.S., Shelton, P.M.L., 1980. The eye margin and compound eye development in the cockroach: evidence against recruitment. J. Embryol. Exp. Morphol. 329–343. Ostrin, E.J., Li, Y., Hoffman, K., Liu, J., Wang, K., Zhang, L., Mardon, G., Chen, R., 2006. Genome-wide identification of direct targets of the Drosophila retinal determination protein Eyeless. Genome Res. 16, 466–476.
on
328
M. Friedrich / Developmental Biology 299 (2006) 310–329
on
al
co
py
Selengut, J.D., Parlikar, B.E., Rebay, I., 2003. The transcription factor Eyes absent is a protein tyrosine phosphatase. Nature 426, 299–302. Treisman, J.E., Rubin, G.M., 1995. Wingless inhibits morphogenetic furrow movement in the Drosophila eye disc. Development 121, 3519–3527. Truman, J.W., Riddiford, L.M., 1999. The origins of insect metamorphosis. Nature 401, 447–452. Truman, J.W., Riddiford, L.M., 2002. Endocrine insights into the evolution of metamorphosis in insects. Annu. Rev. Entomol. 47, 467–500. Ullmann, S.L. (1966). The development of the nervous system and other ectodermal derivatives in Tenebrio Molitor L. (Insecta, Coleoptera). 252. van der Zee, M., Berns, N., Roth, S., 2005. Distinct functions of the Tribolium zerknullt genes in serosa specification and dorsal closure. Curr. Biol. 15, 624–636. White, R.H., 1961. Analysis of the development of the compound eye in the mosquito, Aedes aegypti. J. Exp. Zool. 148, 223–237. Wiersdorff, V., Lecuit, T., Cohen, S.M., Mlodzik, M., 1996. Mad acts downstream of Dpp receptors, revealing a differential requirement for dpp signaling in initiation and propagation of morphogenesis in the Drosophila eye. Development 122, 2153–2162. Wolff, T., Ready, D., 1993. Pattern formation in the Drosophila retina. In: Bate, M., Martinez-Arias, A. (Eds.), The Development of Drosophila Melanogaster, vol. 2. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp. 1277–1326. Yan, H., Canon, J., Banerjee, U., 2003. A transcriptional chain linking eye specification to terminal determination of cone cells in the Drosophila eye. Dev. Biol. 263, 323–329. Yasuyama, K., Meinertzhagen, I.A., 1999. Extraretinal photoreceptors at the compound eye's posterior margin in Drosophila melanogaster. J. Comp. Neurol. 412, 193–202. Younossi-Hartenstein, A., Tepass, U., Hartenstein, V., 1993. Embryonic origin of the imaginal discs of the head of Drosophila melanogaster. Roux's Arch. Dev. Biol. 203, 60–73. Zimmerman, J.E., Bui, Q.T., Liu, H., Bonini, N.M., 2000. Molecular genetic analysis of Drosophila eyes absent mutants reveals an eye enhancer element. Genetics 154, 237–246.
Au
th o
r's
pe
rs
of the zerknullt region of the Antennapedia gene complex in Drosophila. Genes Dev. 1, 1268–1279. Sanchez-Salazar, J., Pletcher, M.T., Bennett, R.L., Brown, S.J., Dandamudi, T.J., Denell, R.E., Doctor, J.S., 1996. The Tribolium decapentaplegic gene is similar in sequence, structure, and expression to the Drosophila dpp gene. Dev. Genes Evol. 206, 237–246. Schmidt-Ott, U., Technau, G.M., 1992. Expression of en and wg in the embryonic head and brain of Drosophila indicates a refolded band of seven segment remnants. Development 116, 111–125. Schroder, R., Eckert, C., Wolff, C., Tautz, D., 2000. Conserved and divergent aspects of terminal patterning in the beetle Tribolium castaneum. Proc. Natl. Acad. Sci. U. S. A. 97, 6591–6596. Seimiya, M., Gehring, W.J., 2000. The Drosophila homeobox gene optix is capable of inducing ectopic eyes by an eyeless-independent mechanism. Development 127, 1879–1886. Serikaku, M.A., O'Tousa, J.E., 1994. Sine oculis is a homeobox gene required for Drosophila visual system development. Genetics 138, 1137–1150. Silver, S.J., Rebay, I., 2005. Signaling circuitries in development: insights from the retinal determination gene network. Development 132, 3–13. Singh, A., Kango-Singh, M., Sun, Y.H., 2002. Eye suppression, a novel function of teashirt, requires Wingless signaling. Development 129, 4271–4280. Steiner, P., 1930. Studien an Panorpa communis. II. Zur Morphologie und postembryonalen Entwicklung des Kopfskeletts von Panorpa communis L. Z. Morphol. Oekol. Tiere 17, 26–67. Suzuki, T., Saigo, K., 2000. Transcriptional regulation of atonal required for Drosophila larval eye development by concerted action of eyes absent, sine oculis and hedgehog signaling independent of fused kinase and cubitus interruptus. Development 127, 1531–1540. Svacha, P., 1992. What are and what are not imaginal disks: reevaluation of some basic concepts (Insecta, Holometabola). Dev. Biol. 154, 101–117. Tomlinson, A., 2003. Patterning the peripheral retina of the fly: decoding a gradient. Dev. Cell 5, 799–809. Tootle, T.L., Silver, S.J., Davies, E.L., Newman, V., Latek, R.R., Mills, I.A.,
329
