Dachshund homologs in other insects

The homolog of the Drosophila gene dachshund (dac) was isolated from the beetle Tribolium castaneum. Tc'dac is expressed in all appendages except urogomphi and pleuropodia. Tc'dac is also active in the head lobes, in the ventral nervous system, in the primordia of the Malpighian tubules and in bilateral stripes corresponding to the presumptive dorsal midline. Expression of Tc'dac in the labrum lends support to the interpretation that the insect labrum is derived from a metameric appendage. The legs of Tribolium accommodate two Tc'dac domains, of which the more distal corresponds to the single dac domain described for Drosophila leg discs. In contrast to Drosophila, where this domain is thought to intercalate between the homothorax (hth) and the Distal-less (Dll) domains, in Tribolium it arises from within the Dll domain. Both the distal Tc'dac domain in the legs as well as the expression in the labrum are deleted in embryos mutant for the Tc'Dll gene, while the proximal leg domain and the mandibular expression are unaffected. Based on Tc'dac expression in wild-type and mutant embryos, serial homology of the complete mandible with the coxa of the thoracic legs has been demonstrated. This homology affirms the gnathobasic nature of the insect mandible (Prpic, 2001).

dac expression in the leg primordia of Tribolium and the imaginal discs of Drosophila is similar. In both species, strong expression of dac appears relatively late during leg development, and at intermediate proximal-distal positions. In mature leg primordia, this dac domain is flanked proximally and distally by the 'ring' and the 'sock' of Dll expression, respectively. Also, a region of overlap between dac and the Dll 'sock' is present in both species. One difference between the Tribolium patterns and those in Drosophila is that distal regions appear to be underrepresented in the beetle leg primordia. While the region of Dll/dac overlap is large in Drosophila,including most of the primordia of tibia and tarsus, in Tribolium this overlap is restricted to a narrow ring. However, this correlates well with the fact that certain distal structures of the adult beetle leg are only formed during metamorphosis. The tibia and the tarsomeres of the imaginal leg are represented in the larva only as a single rather short podomere, termed tibiotarsus. The final number and size of adult podomeres arise in a second growth phase during metamorphosis (Prpic, 2001).

In addition to the difference just mentioned, there are three more discrepancies in dac expression in the embryonic thoracic leg primordia of Tribolium versus the postembryonic imaginal discs of Drosophila . (1) A surprising finding is the presence of an additional proximal domain in the thoracic appendages of Tribolium. In Drosophila, dac is reported to form a single domain in the leg discs. In crustaceans and chelicerates, too, only one dac domain has been observed. Despite its low abundance and although it is not yet known if a proximal dac domain is typical for insect leg primordia in general, it is believed this domain is relevant since its existence provides a rationale for understanding expression and regulation of Tc'dac in the gnathal segments (Prpic, 2001).

(2) A second apparent difference between the expression patterns of Tc'dac and Dm'dac in the leg concerns the position where the (distal) dac domain arises relative to the Dll domain. In Drosophila,it is believed that dac expression intercalates between the hth and Dll domains. The proximal 'ring' of Dll in mature discs is thought to arise as a secondary expression domain once the dac domain has already established itself. In Tribolium, however, it is evident that the distal Tc'dac domain arises within the still unbroken Dll domain, and that increasing abundance of Tc'dac coincides with loss of Tc'Dll expression in these cells, which results in the division of the initial Tc'Dll domain into the proximal 'ring' and distal 'sock' observed at later stages. In other words, the Dll ring in Tribolium is a remnant of the original Tc'Dll domain and not a newly formed, secondary domain. Future work will show if the two species really differ in this expression detail or if persistence of Dll expression proximal to the dac domain has been missed in Drosophila due to the folded architecture of leg imaginal discs. Emergence of the ring-and-sock pattern by downregulation of Dll in intermediate positions has also been described for Schistocerca, suggesting that this mode is ancestral in insects. Since antagonism between dac and Dll occurs in the Drosophila leg, dac may well be required for the generation of the ring-and-sock pattern (Prpic, 2001).

(3) The third difference between Tc'dac and Dm'dac expression in the leg provides an example of how limb patterning during dipteran evolution has adapted to the specific condition of imaginal disc development. In Drosophila,the dac domain is asymmetric along the dorso-ventral axis of the leg imaginal disc. This expression domain can be described as a ring which is much broader dorsally than ventrally. This dorsal expansion correlates with the way femur and tibia form in Drosophila,and how the leg disc evaginates during metamorphosis. Most leg podomeres are derived from ring-shaped primordia in the imaginal disc. During disc eversion, these rings are transformed into podomeres along the elongated leg in a process often compared to the extension of a telescope. However, the first podomeres that exit the disc cavity through its connection to the body wall epidermis are not the distal-most tarsus, but a dorsal lobe of the leg disc which comprises distal femur and proximal tibia -- which both express dac. Only after disc eversion do these two podomers become separated by longitudinal fission. The asymmetric expression of dac in Drosophila appears, therefore, to be an adaptation to the mechanical needs of disc eversion, while the symmetric pattern in Tribolium represents a more simple ancestral situation. It is intriguing to speculate that the need for an asymmetric dac domain may be the reason behind the altered expression of dpp in Drosophila, where the dpp expression domain is greatly expanded dorsally, while it is confined to the distal tip of the appendages in more ancestral arthropods like Tribolium, Schistocerca and Cupiennius (Prpic, 2001).

The labrum expresses Dll in all insects investigated; nevertheless, its metameric nature is still disputed since Dll can be seen as a general marker for structures growing out from the body wall rather than a specific marker for segmental limbs. Based on a homeotic phenotype in adult Tribolium, previous studies have concluded that the labrum was indeed of appendicular origin. Additional molecular evidence for this interpretation is provided by demonstrating that another gene with an essential function in Drosophila leg development, dac, is expressed in the Tribolium labrum. Even though the Tc'dac expression domain in the labrum is incomplete in the sense that it does not form a full ring, its intermediate proximal-distal position -- and its dependence on Dll function -- provides additional support for the labrum indeed being serially homologous to the other metameric arthropod appendages (Prpic, 2001).

It is generally believed that the maxillary and labial palps represent the telopodite of these appendages, while the maxillary stipes, cardo, galea and lacinia, and the labial mentum, prementum and glossae represent the coxopodite. In the labium, Tc'dac is expressed exclusively in the proximal part (which after metamorphosis will form mentum, prementum and glossae), while the labial palp remains free of expression. In Tc'Dll mutants, the labial palp is deleted, but Tc'dac expression remains unaffected. In this respect, the labial Tc'dac expression resembles the proximal expression domain in the thoracic legs. These data strongly suggest that the labial Tc'dac expression domain is actually homologous to the proximal rather than to the distal leg domain (Prpic, 2001).

Tc'dac expression in the maxilla is stronger than in the labium, but also for the maxilla the expression in Tc'Dll mutants makes it clear that most of the expression is in the coxopodite. However, in wild-type animals a small Tc'dac domain forms in the maxillary palp. This domain is missing in Tc'Dll mutant embryos, similar to the distal domain in the legs. This suggests that the palp domain is serially homologous to the distal leg domain, while the major maxillary Tc'dac expression again is homologous to the proximal leg domain. That no distal Tc'dac domain is present in the labial palps concurs with the fact that positional values present in the maxilla are missing in the labium: the maxillary palp in Tribolium larvae has three podomeres, while the labial palp has only two (Prpic, 2001).

It is argued that the expression pattern of dac in Tribolium actually provides evidence for the gnathobasic origin of the mandible, i. e. formed from the limb base. Like the coxopodite domains in leg, maxilla and labium, the Tc'dac expression in the mandible also is independent of Tc'Dll, and the similarity in size and expression of all three gnathal appendages in embryos mutant for Tc'Dll strongly suggests serial homology of the mandible to the coxopodite of maxilla and labium. This line of reasoning also makes it clear that the mandibular Tc'dac expression corresponds to the proximal leg domain, not to the distal domain -- even though it has been upregulated such that it is as strongly active as the distal leg domain. Since the proximal leg domain is located in the coxa, serial homology of coxa, mandible and the coxopodites of maxilla and labium can be inferred. This lends further support to the notion that the insect trochanter is part of the telopodite. Accordingly, the maxillary galea and the labial paraglossa are probably not serial homologs of the trochanter, but represent coxal endites (Prpic, 2001).

In summary, the expression of Tc'dac is strong confirmative evidence in favor of the gnathobasic origin of the mandibles. This interpretation of gnathal Tc'dac expression is based on the presence of a proximal dac domain in the developing Tribolium legs, a domain which apparently is missing in Drosophila. This shows once again the importance of comparative analyses for the correct interpretation of morphological structures and developmental processes. It remains to be seen how the proximal Tc'dac domains in the legs and in the gnathal appendages are regulated, whether they serve similar functions, and to which degree differential regulation of Tc'dac is responsible for the morphological differences among these appendages (Prpic, 2001).

The expression patterns of Gryllus (cricket) homothorax (Gbhth) and dachshund (Gbdac) are described, together with localization of Distal-less or Extradenticle protein during leg development. Their expression patterns have been correlated with the morphological segmentation of the leg bud. The boundary of Gbhth/GbDll subdivision is correlated with the segment boundary of the future trochanter/femur at early stages. Gbdac expression subdivides the leg bud into the presumptive femur and more distal region. During the leg proximodistal formation, although the early expression patterns of GbDll, Gbdac, and Gbhth significantly differ from those of Drosophila imaginal disc, their expression patterns in the fully segmented Gryllus leg are similar to those in the Drosophila late third instar disc (Inoue, 2002).

Although the legs of adult flies and crickets are very similar in their segmental compositions, the developmental processes producing their morphologies are quite distinct. In the Drosophila imaginal disc, leg formation occurs through the concentric folding and the subsequent segmentation of monolayered epithelia in the leg disc during later larval stages, although the early leg disc remains as a flattened two-dimensional structure. In contrast, the cricket leg bud is formed directly from the body wall and segmented during the subsequent outward growth in the early embryogenesis period. The leg segmentation in Gryllus occurs intercalatively step by step until stage 11 (6 days after EL). The changes have been classified into the five following stages: (1) formation of the leg bud at stages 6-7 (2.5 days after EL); (2) the first morphological segmentation at the future trochanter/femur boundary at stage 8 (3 days after EL); (3) the second segmentation in the femur/distal telopodite boundary at stage 9 (4 days after EL); (4) the third segmentation in the tibia/tarsus boundary at stage 10 (5 days after EL); (5) the fourth segmentation at the coxa/trochanter boundary. Then, the elongation of each segment takes place to form the legs of the nymph until hatching (14 days after EL) (Inoue, 2002).

Before the onset of the leg bud formation (stage 5), Gbhth is expressed uniformly throughout the embryos. Just before the onset of leg bud formation (stage 5, 40 h after egg laying), GbDll starts to be expressed in the presumptive thoracic leg region. Subsequently, Gbhth expression was downregulated in the same regions (stage 6, 48 h after egg laying). Thus, the Gbhth/GbDll antagonistic subdomains seem to be established in the early cricket embryos, as observed in Drosophila. In the early stages of leg bud formation (stages 7-9), Gbhth is expressed in the proximal region of the leg bud. In embryos at stages 8-10, when the leg segments are visible, the distal boundary of the Gbhth expression domain is localized at the proximal region of the femur segment (Inoue, 2002).

Expression patterns of Gbdac during leg development are dynamic, although Dmdac is expressed as a single ring in the Drosophila leg imaginal disc throughout its development. Gbdac expression is first detected in an anterior patch of cells in the leg bud at stage 7. At stage 8, the Gbdac expression domain becomes a narrow circumferential ring in the middle of the leg bud. At stage 9, the expression domain divides into two rings. Gbdac expression is not observed in the presumptive intersegmental border between the femur segment and more distal segments. Between stages 10 and 11, the proximal ring of expression corresponds to the distal part of the femur segment, while the distal ring of expression covers a region from the distal tibia to the proximal tarsus segment. In sagittal sections of the metathoracic femur, Gbdac expression is detected in the invaginating apodeme, as well as in the epithelial tissue of the distal femur (Inoue, 2002).

To compare expression patterns of Gbhth and Gbdac with localization of GbDll or GbExd, double staining was performed, using the corresponding RNA probes and an antibody against Dll or Exd, which are used as distal and proximal markers, respectively, in Drosophila, Acheta (Orthoptera, cricket), and Schistocerca (Orthoptera, grasshopper).Prior to the leg bud formation (stage 5), due to weak expression of GbDll, no double stainings could be observed. Prior to the first leg segmentation, Gbhth is expressed in the proximal region of the leg bud, while GbDll is detected in the distal region of the leg bud (stages 6-7). A merged panel reveals that the leg bud is stained with red and green without significant overlap, indicating that the bud is divided into two domains: a distal GbDll-localized domain and a proximal Gbhth-expressing domain. These domains are complementary at this stage, but by the end of stage 7 they partially overlap. At the same stage, GbExd accumulation, caused by nuclear localization of GbExd, is strongly detected in the proximal region of the leg bud, though low levels of GbExd expression can be seen in the distal region. The GbExd accumulation domain in the proximal region overlaps the Gbhth expression domain, as is observed in Drosophila (Inoue, 2002).

The subdivision of the leg bud into proximal and distal domains becomes morphologically discernible as a circumferential constriction, which is the boundary between the trochanter and femur (stage 8). The proximal limit of the GbDll domain corresponds to this boundary at this stage. However, the GbDll domain includes the distal region of the trochanter in later stages (Inoue, 2002).

At stages 8-9, Gbhth is expressed continuously in the proximal domain of the leg bud, overlapping the GbExd accumulation domain. By early stage 8, GbDll is localized throughout the distal tip of the leg bud, including the telopodite. Gbdac is expressed in the middle of the leg bud as a narrow ring, overlapping the GbDll expression domain. GbDll expression starts to become downregulated in the central region at the end of stage 8, in a region where Gbdac is expressed. The domain of GbDll and Gbhth co-expression continues to be observed at stage 9. The proximal ring of GbDll expression, corresponding to the proximal domain of the femur segment, remains unchanged from stage 9 to stage 11 (Inoue, 2002).

By stage 9, the Gbdac expression domain observed at stage 8 has divided into two domains: the proximal and distal domains. Meanwhile GbDll expression becomes undetectable in the middle region. The distal Gbdac domain therefore overlaps a proximal region of the distal GbDll domain, while no such co-expression is observed in the proximal domain. A narrow domain showing no expression of Gbhth, Gbdac, or GbDll can be observed between the two Gbdac domains. Consequently, six proximodistal expression domains appear in the Gryllus leg (Inoue, 2002).

At stage 10, the third morphological segmentation is observed in the distal leg bud, which divides into the tibia and tarsus. Subsequently, the fourth segmentation is discernible in the proximal leg bud, which divides into the coxa and trochanter. It has not been possible to find any of the boundaries of expression of the known appendage genes corresponding of the tibia/tarsus and coxa/trochanter boundaries (Inoue, 2002).

At stages 11-12, following the establishment of the leg segments, structures that connect adjacent segments such as articulates, muscle patterns, etc., are constructed at the segment boundaries. These stages are therefore designated here as the articulation phases. In Gryllus, since the major leg segments can be identified morphologically, the leg segments and the six domains determined by expression patterns of Gbhth, Gbdac, and GbDll can be easily correlated. The proximal-most domain in which only Gbhth is expressed, corresponds to the body wall, coxa segment, and proximal trochanter. The proximal boundary of the GbDll/Gbhth domain lies in the trochanter, and the overlapping GbDll/Gbhth domain extends into the proximal femur. The Gbdac domain corresponds to the middle of the femur segment, including the articulation between the femur and tibia. At stages 11-12, a narrow domain can also be found in which neither GbDll nor Gbdac is expressed, corresponding to the proximal tibia. The Gbdac/GbDll domain includes the articulate between the tibia and tarsus, and extends to the presumptive boundary between tarsal segments 1 and 2. The distal-most GbDll domain corresponds to presumptive tarsal segments 2 and 3 and the pretarsus. The intermediate three expression domains, i.e. the GbDll/Gbhth, Gbdac, and GbDll/Gbdac domains, include the segmental boundaries of the trochanter/femur, the femur/tibia, and the tibia/tarsus, respectively, but do not correspond to the segments (Inoue, 2002).

Expression patterns of Gryllus hth, dac, and Dll in the leg bud with those in the Drosophila leg imaginal disc were compared. The results reveal that these expression domains resolve into similar patterns. In contrast, some differences in the elaborating processes of the expression patterns of the three genes can be seen between Gryllus and Drosophila (Inoue, 2002).

The position of the proximal limit of the GbDll domain has a very sharp boundary between stages 6-8, corresponding to the morphological segmental boundary between the femur and trochanter. Thus, the most proximal segment of the telopodite, i.e. the trochanter, is not included in the GbDll domain in early stages. In contrast, in Drosophila, genetic evidence has demonstrated the subdivision of the leg disc by Dmexd and DmDll into the coxopodite and telopodite. In addition, it has been reported that Dll is detected throughout the telopodite during early development in Acheta (Orthoptera, cricket). Despite these discrepancies, the observations of the expression patterns of GbDll and Gbhth or GbExd in later stages are basically consistent with the results obtained for Acheta, Schistocerca (Orthoptera, grasshopper, and Drosophila (Inoue, 2002).

Following the primary subdivision by GbDll and Gbhth, their expression domains overlap at the boundary at later stages. The domain of Gbhth expression does not strictly correspond to the coxopodite, but expands distally into the femur. This is the same for Drosophila leg, in which the limit of expression of Dmhth expands into the proximal femur. In Drosophila, the first intercalated region between the Dmhth and DmDll domains is the intermediate region expressing Dmdac, and as a result, three discrete domains are established in the leg imaginal disc. In contrast, in Gryllus, three discrete expression domains of the three genes are not observed during leg development (Inoue, 2002).

The expression domain of Gbdac transiently overlaps with that of GbDll at early stages. In Drosophila, Dmdac expression is asymmetrically turned on in dorsal cells that still express DmDll, in the early third instar leg disc. Thus, in both insects, the overlapping Dll/dac domain is observed transiently and subsequently resolves into two domains; proximally Gbdac and distally Gbdac/GbDll in Gryllus, and proximally Dmdac and distally DmDll in Drosophila. At stages 8-9, the GbDll expression fades in the intermediate portion of the leg, and this leads to a new proximal boundary of GbDll. This boundary is correlated with the second segmentation of the femur/distal telopodite. No corresponding expression boundary has been reported in the Drosophila leg imaginal disc. In Drosophila, the expression boundary between the DmDll/Dmdac domain and distal DmDll domain corresponds to that between tarsal segments 1 and 2. Future tarsal segment 1 may be generated in the distal-most region of the Dmdac expression domain. In Gryllus, the distal limit of the Gbdac domain is likely to correspond to the boundary between tarsal segments 1 and 2 (Inoue, 2002).

From these results it was found that the expression patterns of the three genes are essentially conserved between Drosophila and Gryllus, although the time course of the pattern varies according to the developmental mode. The following conclusions were reached: (1) at early stages, expressions of Gbhth and GbDll do not correspond to the future coxopodite and telopodite, but rather to the presumptive trochanter/femur boundary; (2) Gbdac expression subdivides the leg bud into the presumptive femur and more distal region; (3) the expression patterns of GbDll, Gbdac, and Gbhth in the fully segmented Gryllus leg are similar to those in the Drosophila late third instar disc (Inoue, 2002).

The genes Distal-less, dachshund, extradenticle, and homothorax have been shown in Drosophila to be among the earliest genes that define positional values along the proximal-distal (PD) axis of the developing legs. In order to study PD axis formation in the appendages of the pill millipede Glomeris marginata, homologs of these four genes were isolated and their expression patterns examined. In the trunk legs, there are several differences from Drosophila, but the patterns are nevertheless compatible with a conserved role in defining positional values along the PD axis. However, their role in the head appendages is apparently more complex. Distal-less in the mandible and maxilla is expressed in the forming sensory organs and, thus, does not seem to be involved in PD axis patterning. No components of mouthparts could be identified that are homologous to the distal parts of the trunk legs and antennnae. Interestingly, there is also a transient premorphogenetic expression of Distal-less in the second antennal and second maxillary segment, although no appendages are eventually formed in these segments. The dachshund gene is apparently involved both in PD patterning as well as in sensory organ development in the antenna, maxilla, and mandible. Strong dachshund expression is specifically correlated with the tooth-like part of the mandible, a feature that is shared with other mandibulate arthropods. homothorax is expressed in the proximal and medial parts of the legs, while extradenticle RNA is only seen in the proximal region. This overlap of expression corresponds to the functional overlap between extradenticle and homothorax in Drosophila (Prpic, 2003).

In order to reconstruct the evolution of the gene expression pattern, the expression of Dll homologs has been studied in a great number of different arthropod species. This study is the first detailed account of Dll expression in a myriapod and the first report on expression of dac, hth, and exd in a myriapod. The data on Dll presented here show that, in contrast to the antenna and trunk legs, in the two gnathal appendages, mandible and maxilla, no Gm-Dll expression can be found that can be confidently correlated with PD axis formation. This implies that the Glomeris mouthparts lack elements serially homologous to the distal Gm-Dll-expressing parts of the antenna and legs. Thus, both mandible and maxilla are gnathobasic in nature and lack distal parts (telopodite, palp). A gnathobasic mandible traditionally is considered as a synapomorphy of crustaceans, insects, and myriapods, uniting them into a monophyletic Mandibulata. A gnathobasic maxilla, however, is found only in myriapods [apart from Glomeris (diplopod) also the maxilla of chilopods, symphylans, and pauropods apparently lacks a telopodite, to judge from external morphology] and adults of several crustacean species. The maxilla in insects and most crustaceans is not gnathobasic and has a palp (telopodite). This demonstrates that the gnathobasic condition of an appendage can evolve independently by convergence and thus questions the homology of the mandibular gnathobasy in crustaceans, insects, and myriapods. Indeed, recent molecular phylogenies corroborate two monophyletic groups comprising chelicerates and myriapods in one case and crustaceans and insects in the other. This would argue for an independent origin of the gnathobasic mandible in myriapods and the so-called Tetraconata (insects and crustaceans). However, the results with Gm-dac presented in this study support the homology of the gnathobasy in the mandibles of crustaceans, insects, and myriapods. It has been shown previously that expression of dac is very strong in the mandibles of crustaceans and insects. Similarly, strong expression of Gm-dac is seen in the mandible of Glomeris. The role of the strong dac expression in the development of the mandible is unclear, but it seems possible to correlate it with the specific tooth-like morphology of this appendage. Thus, a common genetic mechanism appears to underlie the gnathobasic nature of the mandibles in myriapods, crustaceans, and insects. In contrast to this, no comparable dac expression has been found in the first locomotory leg (L1) in chelicerates. The L1 segment in chelicerates corresponds to the mandibular segment in the other arthropods (Prpic, 2003).

In summary, the results presented here support earlier reports that the mandible in myriapods is indeed gnathobasic. Moreover, the results indicate that the maxilla is also gnathobasic, which is different from insects and most crustaceans and also from chelicerates, which do not possess a single gnathobasic appendage. Strong expression of dac in the mandible in crustaceans, insects, and myriapods suggests that the mandibular morphology is produced by a homologous mechanism and supports the homology of the mandible in all mandibulate arthropods. Although a homologous mandible in crustaceans, insects, and myriapods would support the monophyly of the Mandibulata, it has to be pointed out that a homologous mandible is also compatible with recent molecular phylogenies on the assumption that a true mandible already existed in the last common ancestor of all extant arthropod classes and has been lost secondarily in the chelicerates (Prpic, 2003a).

Leg development in Drosophila has been studied in much detail. However, Drosophila limbs form in the larva as imaginal discs and not during embryogenesis as in most other arthropods. Appendage genes have been analyzed in the spider Cupiennius salei and the beetle Tribolium castaneum. Differences in decapentaplegic expression suggest a different mode of distal morphogen signaling suitable for the specific geometry of growing limb buds. Also, expression of the proximal genes homothorax and extradenticle (exd) is significantly altered: in the spider, exd is restricted to the proximal leg and hth expression extends distally, while in insects, exd is expressed in the entire leg and hth is restricted to proximal parts. This reversal of spatial specificity demonstrates an evolutionary shift, which is nevertheless compatible with a conserved role for this gene pair as instructor of proximal fate. Different expression dynamics of dachshund and Distal-less point to modifications in the regulation of the leg gap gene system. The significance of this finding is discussed in terms of attempts to homologize leg segments in different arthropod classes. Comparison of the expression profiles of H15 and optomotor-blind to the Drosophila patterns suggests modifications also in the dorsal-ventral patterning system of the legs. Together, these results suggest alterations in many components of the leg developmental system, namely proximal-distal and dorsal-ventral patterning, and leg segmentation. Thus, the leg developmental system exhibits a propensity to evolutionary change, which probably forms the basis for the impressive diversity of arthropod leg morphologies (Prpic, 2003b).

Chicken Dachshund homologs

Based on recent data, a new view is emerging that vertebrate Dachshund (Dach) proteins are components of Six1/6 transcription factor-dependent signaling cascades. Although Drosophila data strongly suggest a tight link between Dpp signaling and the Dachshund gene, a functional relationship between vertebrate Dach and BMP signaling remains undemonstrated. Chick Dach1 is shown to interact with the Smad complex and the corepressor mouse Sin3a, thereby acting as a repressor of BMP-mediated transcriptional control. In the limb, this antagonistic action regulates the formation of the apical ectodermal ridge (AER) in both the mesenchyme and the AER itself, and also controls pattern formation along the proximodistal axis of the limb. These data introduce a new paradigm of BMP antagonism during limb development mediated by Dach1, which is now proven to function in different signaling cascades with distinct interacting partners (Kida, 2004).

Mammalian Dachshund homologs