scalloped

DEVELOPMENTAL BIOLOGY

Embryonic

Expression of scalloped is first detected in the cephalic neuroblasts of embryos during germ-band elongation in stage 9. Expression in the PNS is first seen during germ-band retraction [Images](late stage 11). By stage 14, scalloped is observed in the sense organs of the trunk and antennomaxillary complex. sd transcripts accumulate in the supraesophageal ganglion, and later are also seen in a dorsal cluster of peripheral sense organs and in sensory organs of the gnathal buds (Campbell, 1992).

Larval

scalloped transcripts are found in the larval CNS, probably in glia. Expression is also found in wing imaginal discs, where scalloped is required for proper differentiation. Still later, expression in the adult brain is resticted to subsets of cells, some in regions involved in the processing of gustatory information (Campbell, 1992). scalloped is essential for normal taste behavior in Drosophila (Inamdar, 1993).

Effects of Mutation or Deletion

Viable mutants of the scalloped gene exhibit defects that can include gapping of the wing margin and ectopic bristle formation on the wing (Campbell, 1991).

Chip may encode an enhancer-facilitator, acting to facilitate the activity of distal enhancers. The mechanisms allowing remote enhancers to regulate promoters several kilobase pairs away are unknown but are blocked by the Drosophila suppressor of Hairy-wing protein [su(Hw)] that binds to gypsy retrovirus insertions between enhancers and promoters. su(Hw) bound to a gypsy insertion in the cut gene also appears to act interchromosomally to antagonize enhancer-promoter interactions on the homologous chromosome when activity of the Chip gene is reduced. Chip is needed for the wing margin enhancer of cut. The Chip mutation dominantly enhances the mutant phenotypes displayed by partially suppressed gypsy insertions in both cut and Ultrabithorax and is a homozygous larval lethal, indicating that Chip regulates multiple genes. Chip is normally required for wing margin enhancer function of cut because Chip mutations also enhance the cut wing phenotype of a cut mutation and heterozygotes for Chip display cut wing phenotypes when either scalloped or mastermind (mam) are also heterozygous mutant. Both Sc and Mam are known to regulate the cut distal enhancer, but in contrast to sd and mam mutants, Chip mutants display stronger genetic interactions with gypsy insertions than with wing margin enhancer deletions. Thus, in a heterozygous Chip mutant, a heterozygous gypsy insertion in cut displays a cut wing phenotype, whereas a heterozygous enhancer deletion does not. Dependence on the nature of the heterozygous lesion in the regulatory region strongly suggests that Chip directly regulates cut. More strikingly, it indicates that in a Chip heterozygote, a gypsy insertion is more deleterious to enhancer function than deletion of the enhancer. The simplest explanation is that su(Hw) bound to gypsy in one cut allele acts in a transvection-like manner (interchromosomally) to block the wing enhancer in the wild-type cut allele on a second chromosome. This implicates Chip in enhancer-promoter communication (Morcillo, 1997 and references).

Chip was cloned and found to encode a homolog of the recently discovered mouse Nli/Ldb1/Clim-2 and Xenopus Xldb1 proteins, which bind nuclear LIM domain proteins. Chip protein interacts with the LIM domains in the Apterous homeodomain protein, and Chip interacts genetically with apterous, showing that these interactions are important for Apterous function in vivo. Importantly, Chip also appears to have broad functions beyond interactions with LIM domain proteins. Chip is a ubiquitous chromosomal factor required for normal expression of diverse genes at many stages of development. It is suggested that Chip cooperates with different LIM domain proteins and other factors to structurally support remote enhancer-promoter interactions (Morcillo, 1997).

The mechanisms that allow enhancers to activate promoters from thousands of base pairs away are disrupted by the Drosophila Suppressor of Hairy-wing protein (Su[Hw]). Su[Hw] binds a DNA sequence in the gypsy retrotransposon and prevents activation of promoter-enhancers that are distal to a gypsy insertion in a gene without affecting proximal promoter-enhancers. Several observations indicate that SUHW does not affect enhancer-binding activators. Instead, SUHW may interfere with factors that structurally facilitate interactions between an enhancer and promoter. To identify putative enhancer facilitators, a screen for mutations that reduce activity of the remote wing margin enhancer in the cut gene was performed. Mutations in scalloped, mastermind, and a previously unknown gene, Chip, were isolated. A TEA DNA-binding domain in the Scalloped protein binds the wing margin enhancer. Interactions among scalloped, mastermind and Chip mutations indicate that Mastermind and Chip act synergistically with Scalloped to regulate the wing margin enhancer. Chip is essential and also affects expression of a gypsy insertion in Ultrabithorax. Relative to mutations in either scalloped or mastermind, a Chip mutation hypersensitizes the wing margin enhancer in cut to gypsy insertions. Therefore, Chip might encode a target of su(Hw) enhancer-blocking activity (Morcillo, 1996).

The scalloped and vestigial genes are both required for the formation of the Drosophila wing, and recent studies have indicated that they can function as a heterodimeric complex to regulate the expression of downstream target genes. The consequences of complete loss of scalloped function, ectopic expression of scalloped, and ectopic expression of vestigial for the development of the Drosophila wing imaginal disc have been analyzed. Clones of cells mutant for a strong allele of scalloped fail to proliferate within the wing pouch, but grow normally in the wing hinge and notum. Cells overexpressing scalloped fail to proliferate in both notal and wing-blade regions of the disc, and this overexpression induces apoptotic cell death. Clones of cells overexpressing vestigial grow smaller or larger than control clones, depending upon their distance from the dorsal-ventral compartment boundary. These studies highlight the importance of correct scalloped and vestigial expression levels to normal wing development. Studies of vestigial-overexpressing clones also reveal two further aspects of wing development. (1) In the hinge region vestigial exerts both a local inhibition and a long-range induction of wingless expression. These and other observations imply that vestigial-expressing cells in the wing blade organize the development of surrounding wing-hinge cells. (2) Clones of cells overexpressing vestigial exhibit altered cell affinities. The analysis of these clones, together with studies of scalloped mutant clones, implies that scalloped- and vestigial-dependent cell adhesion contributes to separation of the wing blade from the wing hinge and to a gradient of cell affinities along the dorsal-ventral axis of the wing (Liu, 2000).

Clones of cells in imaginal tissues generally adopt very irregular shapes. Strikingly, however, clones of cells that are ectopically expressing Vg are more rounded and have smoother borders than control clones. Similar differences in clone behavior have been observed upon misexpression or mutation of a number of different genes in Drosophila and have been attributed to differences in the affinity of cells for their neighbors. This effect of Vg is evident in the notum, hinge, and proximal regions of the wing, as well as in other imaginal discs. Within the wing region of the disc, the influence of Vg overexpression on clone shape is graded: clones that are near the D-V wing border generally continue to have irregular shapes, while clones that are far from the D-V border are more circular. This effect was quantified by calculating the circularity of 117 Vg-expressing clones and then plotting the circularity of each clone against its relative distance from the D-V wing border. Circularity is a ratio of clone area to the square of the clone perimeter. The average circularity of VG-expressing clones increases with distance from the D-V border. The observation that the same, constitutive level of Vg expression induces graded changes in clone shape that depend upon clone location suggests that there are normally graded differences in Sd:Vg-dependent cell affinities. Three aspects of the behavior of sd clones in the wing blade are consistent with the hypothesis that reduction in normal Sd:Vg function also influences cell affinity. (1) In the few instances in which relatively large sd clones were recovered, they tended to be more rounded than their wild-type twins. (2) Over a quarter of the sd clones recovered in the wing pouch were associated with multiple wild-type 'twin' clones. Although in some cases this may occur fortuitously, it is also suggested that affinity differences with surrounding wild-type cells could force independent mutant clones into a coherent patch. (3) sd clones tend to be located farther from the D-V boundary than their wild-type twins. Differential location between mutant and wild-type twins has also been observed in the wing for shaggy mutant clones and in the abdomen for patched and smoothened mutant clones, and in both cases it has been hypothesized to derive from differences in cell affinity (Liu, 2000).

While previous studies have emphasized the autonomous requirement for vg in wing development, these results make clear that this autonomous requirement is restricted to the wing blade and that Sd:Vg has an additional, nonautonomous role in promoting the development of the wing hinge. Null alleles of vg delete the wing blade and most, or sometimes all, of the wing hinge. Even when vg mutant animals retain some hinge tissue, a significant amount of tissue is deleted proximal to the inner Wg expression ring. However, by making clones of cells mutant for sd, it was found that Sd:Vg is autonomously required only distal to the inner Wg expression ring. Similarly, clones of cells that are mutant for a null allele of vg grow normally in the notum, but fail to grow in the wing. The precise border where vg is autonomously required maps to the edge of detectable Vg expression. This places the border distal to the inner Wg expression ring. Altogether, these results suggest that Sd:Vg is required nonautonomously for normal development of the wing hinge. Indeed, clones of cells ectopically expressing Vg frequently reorganize the patterning of surrounding tissue in the wing hinge. This reorganization is visible through changes in the expression of Wg and Nubbin, as well as changes in the folding of the disc epithelia. These studies, along with reports on the function and regulation of hth in the hinge, lead to a model for the regulatory interactions between wing hinge and wing blade (Liu, 2000).

The observation that Sd:Vg is both required nonautonomously for normal hinge development and sufficient to reorganize the normal patterning of surrounding hinge tissue leads to the hypothesis that Sd:Vg-expressing wing blade cells produce a signal (X) that influences gene expression in surrounding wing-hinge cells. Ultimately, one key target of this signal is the inner ring of Wg hinge expression. Wg is essential for wing hinge development; Wg expression is induced non-autonomously by Sd:Vg, and normal Wg hinge expression is reduced or absent in vg mutants. The detection of a spot of Wg expression in some vg mutant discs that appears to correspond to a portion of the inner hinge ring implies that the hypothesized signal X may not be absolutely required for Wg expression. Instead, it may function to maintain and promote Wg hinge expression as the wing pouch grows. Alternatively, it may be, as suggested by the failure of Vg-expressing clones to effectively induce Wg hinge expression near the D-V boundary, that Wg hinge expression near the D-V boundary is regulated by a Vg-independent mechanism, which continues to promote a spot of Wg expression even in vg mutants (Liu, 2000). Although the identity of the signal X is not yet known, nor how direct its regulatory influence on Wg may be, it can be inferred that its action ultimately impinges on enhancers within a 1.2-kb fragment of the wg gene identified as being responsible for the distal ring of Wg hinge expression. Recent studies of Drosophila leg development have implied the existence of signaling from proximal cells to distal cells. Thus, in both legs and wings, normal appendage development appears to rely not just on the direct interpretation of primary signals produced along compartment boundaries, but also on secondary signaling between cells in different domains along the proximal-distal axis (Liu, 2000).

While these studies imply that a Sd:Vg-dependent signal is essential for normal hinge development, hinge cells are uniquely competent to express Wg in response to this signal. This implies that a distinct hinge fate precedes receipt of the signal. In addition, a small amount of wing-hinge tissue, and in some cases Wg expression, remains in vg null mutants. Signaling from the wing blade does not therefore act as an inducer of wing-hinge fate per se, but rather acts to elaborate the patterning and growth of the hinge. hth plays a key role in hinge development, and recent studies have demonstrated that hth is essential for Wg expression in the hinge. Thus Hth, together with its partner protein Extradenticle (Exd), may be at least partially responsible for the distinct responsiveness of hinge cells to Sd:Vg-dependent signaling. Hth expression is itself positively regulated by Wg, and thus the distinct fates of both the wing blade and the wing hinge are maintained in part by positive regulatory loops with Wg. Separate blade and hinge territories are also maintained in part by repressive interactions between Sd:Vg and Exd:Hth. However, while the repression of Hth by Sd:Vg is autonomous, and thus may be direct, Hth does not repress Sd:Vg directly, but instead represses Wg expression along the D-V border, which then indirectly limits Sd:Vg expression (Liu, 2000).

The Drosophila homolog of the human TEF-1 gene, scalloped (sd), is required for wing development. The Sd protein forms part of a transcriptional activation complex with the protein encoded by vestigial (vg) that, in turn, activates target genes important for wing formation. One sd function involves a regulatory feedback loop with vg and wingless (wg) that is essential in this process. The dorsal-ventral (D/V) margin-specific expression of wg is lost in sd mutant wing discs, while the hinge-specific expression appears normal. In the context of wing development, a vg::sd TEA domain fusion produces a protein that mimics the wild-type SD/VG complex and restores the D/V boundary-specific expression of wg in a sd mutant background. Further, targeted expression of wg at the D/V boundary in the wing disc is able to partially rescue the sd mutant phenotype. It is inferred from this that sd could function in either the maintenance or induction of wg at the D/V border. Another functional role for sd is the establishment of sensory organ precursors (SOP) of the peripheral nervous system at the wing margin. Thus, the relationship between sd and senseless (sens) in the development of these cells was also examined, and it appears that sd must be functional for proper sens expression, and ultimately, for sensory organ precursor development (Srivastiva, 2003).

When the sd gene is mutated, the phenotype includes not only the wing margins but also the sensory organs that are found at the wing margins. In addition to the loss of wing margin bristles, there is also a reduction in the number of cells, which results in notching of the wings. This reduction in the number of cells is thought to be a result of apoptosis. In addition, overexpression of sd is also associated with apoptotic cell death. Lyra (Ly) mutations, in contrast, result in the loss of the anterior and posterior margin bristles and this is not associated with apoptotic cell death. However, there is a reduction in the number of cells in the wing margin that manifests itself by erosion of the wing margin. Ly mutations have been shown to be dominant gain of function alleles of sens, in that in a Ly background sens is ectopically expressed. To see if Ly and sd interact genetically, wings were examined from sd^ETX4 males that were also heterozygous for Ly. Flies harboring mutants of both genes show a significant enhancement of the wing phenotype compared to flies with either mutant alone. In the transheterozygous fly, the margin bristles are completely absent, suggesting that these two genes work through a common pathway (Srivastiva, 2003).

Because Ly mutations are gain of function alleles of sens and because Ly interacts with sd, it is possible that this could result in alterations of Sens protein levels in sd mutant wing discs. Wing discs derived from wild-type flies and from flies harboring sd⁵⁸ were stained with an anti-Sens antibody. In wild-type discs, Sens is localized to the region fated to become the wing margin with higher levels at the anterior margin in SOP cells. In addition, sens is also expressed in other SOPs distributed throughout the wing disc. In sd⁵⁸ discs, the wing margin-specific expression of sens is completely lost, but expression in other SOPs is unaffected. Substantial margin-specific expression is restored when the vg::sd TEA fusion construct is expressed in sd⁵⁸ discs using a vg-Gal4 driver. That this restoration of Sens is not complete could be attributed to the amount of the fusion VG::SD TEA protein being produced from the transgene. However, this level of restoration is consistent with the notion that the fusion construct can restore the margin-specific expression of wg, and emphasizes the involvement of wg in specifying the formation of SOPs. The mutual enhancement of mutant wing phenotypes by sd and Ly mutations can also be explained based on the role of wg in SOP formation. Because sd mutations affect the margin-specific expression of wg, and in Ly mutations there is a repression of wg expression, it is predictable that in transheterozygotes the overall Wg signal is further reduced at the margin, resulting in the phenotypic enhancement of wing margin loss (Srivastiva, 2003).

sens has been shown to be both necessary and sufficient for the formation of organs of the peripheral nervous system (PNS). Ectopic expression of sens can result in the formation of extrasensory bristles on the wing and thorax. This ectopic formation of sensory bristles can also happen in the absence of genes of the achaete-scute complex, though to a lesser extent. To see if sd has any role in formation of sensory bristles by ectopic expression of sens, and to confirm that sens is necessary and sufficient for formation of the sensory bristles, sens was expressed in a sd mutant background. The UAS-sens transgene was expressed in both sd^ETX4 and sd⁵⁸ mutant backgrounds using a vg-Gal4 driver and expression from the UAS-sens transgene was determined by staining wing discs with the anti-Sens antibody as a control. If sd has no role in ectopic bristle formation by sens, then expression of sens should result in formation of the sensory bristles missing in the margin of the sd mutants. However, sens expression is unable to restore the margin-specific bristles in sd mutants, suggesting that sens may need sd function for formation of bristles and for proper SOP differentiation. Instead of the formation of ectopic bristles, expression of sens in sd^ETX4 enhances the wing phenotype to resemble the result of the enhancement of sd^ETX4 caused by a Ly mutant. To test this further, UAS-sens was also expressed under the control of a dpp-Gal4 construct that drives expression at the A/P compartment border away from the margin. Wild-type wings expressing sens at the A/P border fail to inflate properly upon eclosion but exhibit numerous ectopic bristles at the position of the A/P border as well as numerous ectopic bristles on the thorax. Expression of sens in a sd⁵⁸ mutant background, however, results in very little to no ectopic bristle formation at the A/P border, again suggesting that sens possibly needs sd function for formation of SOPs (Srivastiva, 2003).

In conclusion, a further characterization of the functions of the SD/VG complex during wing development is reported by analyzing the roles of sd, via the vg::sdTEA fusion during patterning by wg, during growth and during SOP development. In the narrow context of the D/V specific expression of wg, the SD/VG complex appears to act upstream of wg as evidenced by the rescue of the D/V WG stripe by the fusion construct and the rescue of sd wing mutations by the expression of exogenous WG. In addition, the relationship between sd and sens in the development of margin-specific bristles is clarified and the results show that sens needs sd function for proper development of the PNS organs. The current model for actions of the SD/VG complex during wing development, incorporating the new data herein, is that the SD/VG complex either induces or maintains the expression of Wg. This, in turn, causes expression of Sd and Vg to promote cell proliferation in the wing pouch. At the D/V boundary Wg also mediates the expression of sens via its actions on the achaete scute (AS-C) complex that, in the presence of Sd, helps to specify the SOP fate (Srivastiva, 2003).

Molecular and functional analysis of scalloped recessive lethal alleles in Drosophila

The Drosophila scalloped (sd) gene is a homolog of the human TEF-1 gene and is a member of the TEA/ATTS domain-containing family of transcription factors. In Drosophila, sd is involved in wing development as well as neural development. Data are presented from a molecular analysis of five recessive lethal sd alleles. Only one of these alleles complements a viable allele associated with an sd mutant wing phenotype, suggesting that functions important for wing development are compromised by the noncomplementing alleles. Two of the wing noncomplementing alleles have mutations that help to define a Vg-binding domain for the Sd protein in vivo, and another noncomplementing allele has a lesion within the TEA DNA-binding domain. The Vg-binding domain overlaps with a domain important for viability of the fly, since two of the sd lethal lesions are located there. The fifth lethal affects a yet undefined motif lying just outside the Vg-binding domain in the C-terminal direction that affects both wing phenotype and viability. This is the first example linking mutations affecting specific amino acids in the Sd protein with phenotypic consequences for the organism (Srivastava, 2004).

Four of the five lethal alleles studied affect the wing phenotype: the physical lesions associated with three of these four are within the C-terminal half of SD and are localized between amino acids 232 and 355. Two of these mutations help define a Vestigial binding domain (VBD) in vivo that overlaps a domain previously predicted by in vitro experiments to be responsible for binding Vg. The sd^3L and sd^47M lesions are within this predicted domain and, due to the molecular nature of these mutations, are predicted to abolish the VBD completely. The sd^68L lesion is located just outside and 3' to this domain but also affects Vg localization in vivo to some extent. This conclusion is supported by the observation that the wing phenotype produced from these two alleles when heterozygous with sd^ETX4 is more severe than the sd^68L/sd^ETX4 phenotype. Since the lesions in sd^3L and sd^47M would also be expected to abolish all aspects of Sd function C terminal to the respective lesion, this could also account for the early recessive lethal phenotype of these two alleles. The sd^68L lesion is only a missense mutation so it would not be surprising if some sd function is retained. Although the sd^68L lesion is located just outside and 3' to the predicted VBD, it is associated with the mutation of tyrosine, an amino acid that is often subject to phosphorylation and dephosphorylation. Phosphorylation-based mechanisms are known to play a role in a great many interactions between proteins. For example, the sd^68L lesion is in the vicinity of a domain where phosphorylation is known to modulate RTEF-1 function in cardiac muscle. Therefore, it initially seemed that the simplest interpretation of the results for the sd^68L allele was that it also directly affected the VBD. However, this now seems unlikely. The partial mislocalization of Vg could also result from reduced Sd levels due to protein instability or even from mislocalization of Sd itself. It is also possible that other protein factors present in vivo are important in regulating the kinetics of Sd binding to Vg or play a vital role in Sd stability. In an sd^68L/+ heterozygote, regulation of this binding or Sd stability could be inefficient and result in the observed variability of the wing complementation phenotype with this allele. The wing phenotype of sd^68L in trans with the more severe but phenotypically stable sd⁵⁸ allele is nonvariable, but still less severe than that produced by sd^3L or sd^47M over sd^58d. Thus, it appears that the sd^68L allele provides some wild-type function, with respect to wing development, in a genetic background shared with the sd^ETX4 or sd⁵⁸ alleles. However, since sd^68L is a recessive lethal, the lesion also compromises some as yet unknown vital function as well. The most likely reason for complementation of the wing phenotype with sd^11L is that the lesion does not affect the VBD because it is more distally located: 78 amino acids from the sd^68L mutation and only eight residues from the C-terminal end of Sd. Moreover, it has been reported that the TEF-1 sequence (Sd homolog) from residue 329 to the C terminus is dispensable with respect to its ability to interact with the TDU protein (Vg homolog) even though high sequence conservation exists throughout this region. Further support for the mutations in sd^3L and sd^47M affecting the VBD and sd^11L not affecting this domain comes from observing Vg localization data from wing discs derived from sd^11L hemizygous larvae as well as from Vg localization in mitotic clones of the sd^47M allele. Vg localization in sd^68L wing discs and in sd mutant clones harboring the sd^47M allele is diffuse rather than nuclear. This is a clear indication that the VBD (in sd^47L) or a related role (as in sd^68L) must not be fully functional, even though in vitro data indicate that sd^68L is not defective in binding Vg. However, Vg in sd^11L wing discs is entirely nuclear, supporting the conclusion that in this allele the VBD is unaffected, while still implicating the region in an alternative function that is essential for viability (Srivastava, 2004).

To date, knowledge about the TEA DNA-binding domain has been based primarily on in vitro mutational analysis. However, extrapolation from in vitro observations to in vivo functions is not always valid. A mutation has been identified within the conserved TEA DNA-binding domain that affects both the essential and the wing-specific functions of sd. The TEA DNA-binding domain has been predicted to have three alpha-helices. However, the limits of the third helix within the domain are not very well defined. The mutation associated with the sd^31H allele (Arg to Lys) is located in the TEA DNA-binding domain between the second and third predicted helices. This lesion also lies between two putative phosphorylation sites, and the role of phosphorylation in regulation of DNA binding by the TEA domain from organisms other than Drosophila has been well documented. The cause of the observed heterozygous wing and homozygous lethal phenotypes associated with this allele can be explained in at least two ways. The phenotypes could simply be the result of a defect induced by this mutation in the regulation of DNA binding by phosphorylation. The second and the third helices of the TEA DNA-binding domain may actually be responsible for contacting the DNA so this mutation could directly affect the ability of Sd to contact DNA, thereby preventing transcription of essential and wing-specific genes controlled by sd. Alternatively, it is also possible that the mutation in sd^31H affects the nuclear localization signal that overlaps the TEA DNA-binding domain of Sd, so that Sd is prevented from entering the nucleus. In the absence of an Sd antibody, it cannot be determined if the mutation prevents Sd from entering the nucleus or simply results in inefficient binding of the protein to its targets in the nucleus. Either of the above putative defects could explain the recessive lethality caused by sd^31H. The late pupal lethality associated with this allele is consistent with an argument that this mutation results in inefficient transport of Sd to the nucleus. The mutant animal is able to survive until the pupal stage, beyond which the level of Sd in the nucleus would be unable to sustain the level of transcription needed for survival. However, Vg localization data from sd^31H mutant discs argue against a defect in nuclear localization of Sd. Because Sd is needed for maintenance of vg and sd expression, one would expect to see some Vg in the wing pouch of the mutant discs if the mutation was simply causing inefficient nuclear localization of Sd. The absence of any noticeable Vg in the wing pouch favors the hypothesis that the mutation affects the DNA-binding ability of the TEA domain. So, this mutant Sd would then not bind its cognate regulatory DNA elements and, as a result, Vg expression in the wing pouch would not be maintained. It is also possible that the absence of Vg in the wing pouch area of the sd^31H disc is merely a consequence of autoregulation in this system (Srivastava, 2004).

While specific lesions have been identified in each of the sd lethal alleles and these have been correlated with phenotypic consequences for the organism, the molecular reason for lethality has not been solved in every case. Since sd^31H has a lesion in the TEA domain, it is relatively easy to understand why this may result in lethality. Similarly, the lethality associated with sd^3L and sd^47M is explicable because of the molecular nature of the lesions: all Sd function downstream of the respective lesion would be abolished. The reasons for the lethality associated with sd^68L and sd^11L are still not obvious. Evidence is provided that the lesion in sd^68L affects wing development and also compromises a vital function, while sd^11L does not appear to affect wing development but does compromise a vital function. The current hypothesis is that these two sd lethal alleles likely affect residues within a domain that is necessary for binding cofactors involved in other critical developmental functions of Sd. Future efforts will concentrate on attempting to identify these putative cofactors (Srivastava, 2004).

The data presented here are relevant to several aspects of Sd function. This study reports the molecular characterization of lethal alleles of sd and this analysis has enabled the association of specific conserved residues within the Sd protein sequence with specific mutant phenotypes. The results have helped to define a VBD in Sd by in vivo criteria. A mutation within the Sd-TEA DNA-binding domain has been shown to be important for both wing development and viability of the fly. Because the residues affected in the sd lethal alleles are conserved across species and phyla, this study could also have important implications for understanding the properties of the vertebrate homolog TEF-1 (Srivastava, 2004).

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date revised: 26 December 2006 

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