Msc, Multiple sex comb
transcription factor - homeodomain - Antp class - required for labial and first thoracic segment development - expressed in the embryonic labial and first thoracic segments - in the absence of Scr expression the first prothoracic segment is transformed to a second mesothoracic identity and the labial palps to maxillary
Gene model reviewed during 5.50
gene_with_stop_codon_read_through ; SO:0000697
Double stop-codon suppression (UAG, UAG) postulated; FBrf0234051 and FlyBase analysis.
Gene model reviewed during 6.25
Triple stop-codon suppression (UAG, UAG, UGA) postulated; FBrf0243886 and FlyBase analysis.
Gene model reviewed during 6.32
Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\Scr using the Feature Mapper tool.
In extended germ band stage embryos, pre-mRNA transcripts of Scr can be found in both the labial segment and, less abundantly, in the anterior half of the prothoracic segment. In contrast, Scr protein expression is limited to the labial segment.
Scr is normally expressed in the labial segment and the dorsolateral part of the prothoracic segment after germband elongation. In a tsh mutant, Scr is ectopically expressed in the ventral ectoderm of the prothorax.
During embryogenesis, Scr transcript is first detected at the start of gastrulation in a 3-4 cell wide band just posterior to the cephalic furrow. At the extended germ band stage, Scr transcript is detected in both layers of the ectoderm of the labial segment, as well as in the anterior portion of the outer ectodermal layer and the mesoderm of the first thoracic segment. This pattern is still detected at the start of germ band contraction, but additional hybridization is detected throughout the outer ectodermal layer of the first th racic segment. After the start of head involution, Scr transcript accumulates in a pattern similar to that of Scr protein, with grains detected in a subset of the ventral nerve cord, wall of the anterior midgut, and continued epidermal labeling in labial and first thoracic segments.
In the cellular blastoderm, Scr transcripts are located in a band 3-4 cells wide located adjacent to the band of Dfd expression. The band of expression is present only in lateral and dorsal parts of the embryo. Lower levels of expression are observed in six additional bands spaced at double segment intervals posterior to the main band of expresssion. Using en as a marker, the main band of Scr expression was localized to parasegment 2. The more posterior expression is thought to correspond to the remaining even-numbered parasegments. In stages 9-10, Scr transcripts accumulate in ectodermal cells of PS2 but not in the overlying mesoderm but do accumulate in mesoderm overlying PS3. By stage 11, the entire labial bud expresses Scr. There is a gradient of Scr expression across PS3 with the strongest expression in the area closest to PS2. Scr expression is also seen in neural derivatives of PS3 and at a lower level in PS6-12. Scr is expressed in the mesoderm of PS3 at stage 11 in both somatic and visceral components. Expression is seen at stage 12 in all myoblasts of T1 and in a portion of the mesoderm surrounding the anterior midgut. This pattern persists until hatching. Later some expression is seen in visceral mesoderm of the posterior midgut. In larvae, exrpession is observed in the labial, and dorsal and ventral prothoracic discs. In addition, some cells of the wing and second leg disc express Scr. Their position suggests that they are adepithelial cells.
Scr transcripts accumulate ventrally in the labial and prothoracic segments in germband extended embryos. Following germ band retraction, signal is detected in the nervous system, particularly in the suboesophageal and prothoracic ganglion, as well as in the pharynx.
Scr transcripts accumulate on the anterior ventral side of the embryo at stage 5 in a region that corresponds to the labial and prothoracic segments on the fate map. After germ band retraction, the strongest expression is observed in the suboesophageal ganglion and the anterior part of the prothoracic ganglion. Weaker staining is observed over the entire nervous system and brain. Strong labelling is also seen in the region of the pharynx.
D. melanogaster shows noticeable sexual dimorphism in its Scr expression pattern The prothoracic Scr expression domain in males extends upto the distal border of the metatarsus, whereas in case of female foreleg pupal disc, the expression will not extend to the distal margin.
Scr protein is located in the cytoplasm prior to embryonic stage 9 and is then nuclear.
In late non-wandering third instar larvae, high levels of Scr protein are detectable in the distal tibia and first tarsal segment region of the leg disc. Low expression is present in the rest of the disc. At 24hr APF, when sex comb rotation is complete, dsx and Scr develop roughly complementary expression patterns in the male leg. dsx is highest in the sex comb teeth and surrounding epidermal cells, while Scr expression is low or absent in sex comb teeth but highest in adjacent epidermal cells. The pattern is maintained at later stages. In females, dsx expression becomes very low or undetectable, and Scr expression in the distal first tarsal segment is much lower than in males.
In addition to expression in the labial and prothoracic ectoderm, the PS2 and PS3 regions of the CNS, and the visceral mesoderm of the anterior and posterior midgut, expression is observed in three new locations. These are a 4-cell-wide stripe in the ectoderm at stage 5 that partially overlaps the posterior edge of the maxillary en stripe, the embryonic salivary gland, and the dorsal ridge.
As observed previously, Scr antibodies stain the labial and prothoracic ectoderm, the 2nd and 3rd parasegments of the CNS, and the visceral mesoderm of the anterior and posterior midguts. A new antibody allowed the detection of weaker sites of expression in the precursors of the larval salivary glands, the dorsal ridge, and a stripe of ectodermal cells in the parasegment 2 region of stage 5 embryos.
dpp and Scr proteins are expressed in adjacent non-overlapping domains in the visceral mesoderm, the Scr domain being posterior to the dpp domain. In dpps21/s2 mutants, the Scr domain is expanded anteriorly to encompass the visceral mesoderm cells that give rise to the gastric caeca which normally express dpp.
Scr protein is expressed in the visceral mesoderm close to the anterior tip of the midgut. At stage 13, the domain of expression extends to about 4 nuclei along the AP axis and spans the width of the visceral mesoderm. By stage 14, the domain has elongated to 6 nuclei and has split into dorsal and ventral patches on each side of the body. By stage 17, the patches of Scr expressing nuclei have stretched posteriorly over the midgut to form 4 rows, each starting at the base of a gastric caecum. The number of cells expressing Scr and the level of expression are significantly reduced in an Antp- background.
During embryogenesis, Scr protein is detected in the epidermis, in the nervous system, and in the visceral mesoderm. Scr protein is first detected in 3 hour embryos, in a band posterior to the cephalic furrow (parasegment 2). During germ band extension, label moves posteriorly 6-8 cells. Scr protein becomes visible in parasegment 3, in the lateral portion of the ectoderm, and in the mesoderm. Later in the extended germ band stage, labeling spreads in what is now the prothoracic segment. During germ band retraction, Scr protein is visible in the central nervous system and the visceral mesoderm, as well as in the labial and prothoracic segments. In stage 16 embryos, Scr protein is detected in a single segment-width of cells in the CNS.
Scr protein is first detected at early germ band retraction stage in a 4-5 cell width stripe in the midgut visceral mesoderm of parasegment 4. At later stages, this stripe expands to 6-7 cell widths, extending just anterior and just posterior to parasegment 4.
Scr protein is expressed in a slightly extended domain in homozygous ftz mutant embryos. Embryos homozygous for eve3 showed no Scr protein staining but there is some staining in embryos homozygous for eve4. Normal homeotic gene function is seen in embryos homozygous for en59, en54, en55, wgl-17, h41, odd5, prd4 and runB102. For an unknown reason, embryos homozygous for opa1 have a lack of Scr protein activity. No Scr gene expression is seen in ftz,prd or opa,prd double mutant embryos and there is normal staining in odd,eve double mutant embryos. The Scr protein domain is slightly extended in kni mutants and KrB206 mutants but missing in hb mutants.
During embryogenesis, Scr protein is first detected at the extended germ band stage in nuclei within the labial segment, and in the yolk mass. At the start of germ band contraction, it is detected within the first thoracic segment, in a band of nuclei along the anterior portion, and continues to be detected in labial nuclei. At the start of dorsal closure, Scr protein is detected in more nuclei in the anterior half of the first thoracic segment. When germ band contraction is complete, nuclei throughout the epidermis of the labial an first thoracic segments accumulate Scr protein; this staining continues past the completion of head involution. CNS expression of Scr protein is first detected at the start of head involution, in two regions of the ventral nerve cord: in a large group of nuclei within the posterior part of the subesophageal ganglia and 2-6 nuclei in the next more posterior segment. This staining continues past the completion of head involution. Scr protein is also detected in the midgut. In larvae and adults, Scr protein is found in the subesophageal ganglia. Larval staining is also detected in lab al and first thoracic imaginal discs, with faint staining observed in second and third thoracic leg discs.
Scr protein is detected in stages 11 and 12 in ectodermal cells of the parasegment 2 and 3 primordia. During stage 12 strong expression is observed in the labial lobes. After head involution initiates, Scr protein becomes visible in the posterior portion of the suboesophageal ganglion and in two small, paired clusters of cells in the first thoracic ganglion.
GBrowse - Visual display of RNA-Seq signalsView Dmel\Scr in GBrowse 2
Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete
Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see GBrowse for alignment of the cDNAs and ESTs to the gene model.
For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.
Source for identity of: Scr CG1030
Haploinsufficient locus (not associated with strong haplolethality or haplosterility).
RNAi generated by PCR using primers directed to this gene causes a cell growth and viability phenotype when assayed in Kc167 and S2R+ cells.
Transvection at the Scr gene is blocked by rearrangements that disrupt pairing, but is z independent. Silencing of the Scr gene in the second and third thoracic segments is disrupted by most chromosomal aberrations within the Scr gene.
Candidate gene for quantitative trait (QTL) locus determining bristle number.
The amino terminal of the Scr homeodomain is necessary for the specific activation of the fkh 37bp fkh250 element in vivo. Scr negatively regulates hth, which is required for the nuclear localization of the exd gene product.
exd protein localised to the nucleus is proposed to suppress tarsus development and activate arista development. In the mesodermal adepithelial cells of the leg imaginal discs, Scr protein is proposed to be required for the synthesis of a tarsus-inducer that when secreted acts on the ectoderm cells inhibiting nuclear accumulation of exd protein, such that tarsus determination is no longer suppressed and arista determination is no longer activated.
Scr activity is required cell nonautonomously for tarsus determination. Specifically, Scr activity is required in the mesodermal adepithelial cells of all leg imaginal discs at late second/early third larval stage for the synthesis of a mesoderm-specific, tarsus inducing, signaling factor, which after secretion from the adepithelial cells acts on the overlaying ectodermal cells determining tarsus identity.
Simultaneous removal of pb and Scr activity results in a proboscis-to-antenna transformation. Dominant negative pb molecules inhibit the activity of Scr indicating that pb and Scr interact in a multimeric protein complex in determination of proboscis identity. The absence of pb and Scr expression leads to antennal identity, expression of pb only leads to maxillary palp identity, expression of Scr only leads to tarsus identity and the expression of both pb and Scr leads to proboscis identity.
The pattern of Scr expression during the embryonic development of D.melanogaster (Diptera), T.domestica (Thysanura, firebrats), O.fasciatus (Hemiptera, milkweed bug) and A.domestica (Orthoptera, cricket) is compared. Mapping both gene expression patterns and morphological characters onto the insect phylogenetic tree demonstrates that in the cases of wing suppression and comb formation the appearance of expression of Scr in the prothorax apparently precedes these specific functions.
Mutations show weak interactions with high and low selection lines, abdominal and sternopleural bristle numbers are affected. Results suggest Scr is in the same genetic pathway as bristle number quantitative trait loci (QTL).
Analysis of the distribution of certain gene products in embryos lacking Scr and cuticular phenotypes of embryos with mutations that blocked head involution suggests that Scr mutant embryos do not exhibit a labial to maxillary transformation, but instead lack of Scr function causes a loss of labial identity.
A phylogenetic analysis of the Antp-class of homeodomains in nematode, Drosophila, amphioxus, mouse and human indicates that the 13 cognate group genes of this family can be divided into two major groups. Genes that are phylogenetically close are also closely located on the chromosome, suggesting that the colinearity between gene expression and gene arrangement was generated by successive tandem gene duplications and that the gene arrangement has been maintained by some sort of selection.
Ecol\lacZ reporter gene constructs have demonstrated that many of the Scr enhancers are located closer to the ftz promoter than to the Scr promoter, yet the expression patterns of the two genes do not overlap. The region carries ftz enhancers and repressor binding sites and Scr anterior\posterior midgut enhancer. The sequences in this region may be involved in preventing Scr enhancers from activating the ftz promoter.
It has been previously reported that Scr embryos display partial transformation of the labial segment to a more anterior maxillary identity. This transformation seems unusual because the Dfd protein does not accumulate in the labial cells of an Scr mutant. It is proposed that the putative ectopic maxillary sense organ in Scr mutants may instead be the labial sensory organ which is now visible because of incomplete head involution.
The 75kb regulatory region of Scr has been dissected and tested in Ecol\lacZ reporter constructs for expression patterns. Scr expression in some tissues appears to be controlled by multiple regulatory elements that are separated, in some cases, by more than 20kb of intervening DNA. Regulatory sequences that direct reporter gene expression in an Scr-like pattern in the anterior and posterior midgut are embedded in the regulatory region of the ftz gene.
Regulation of Scr in the labial segment and in the CNS requires the apparently synergistic action of multiple, widely spaced enhancer elements. Regulation in the prothorax also appears to be controlled by multiple enhancers, one complete pattern element and one subpattern element. Scr regulation in the visceral mesoderm is controlled by an enhancer(s) located in only one DNA fragment.
Expression of Scr in C.elegans demonstrates the specificity of function of the Drosophila and C.elegans Hox proteins is conserved in an assay to control the anterior versus posterior migration of Q-cell decendents. The Drosophila protein can substitute the normal function of the C.elegans protein in three different cell-fate decisions.
The authors name enhancer trap inserts, as e.g. l(3)N33, for which the lethality does not map to the P insert, but have not come up with a _gene_ name. 'Excision' derivatives generate lethals in two additional complementation groups, though in 4/5 derivatives the P elements have locally hopped rather than simply excised. In view of this it is premature to be naming genes, though mulspcons can be named.
An Scr-regulated salivary gland gene has been identified by enhancer trapping in cytological region 85D.
Restrictions on Scr protein activity are imposed by different genes in different tissues. Bithorax complex homeotic genes (excluding Ubx and abd-A) limit Scr transcription and function in the cuticle. Salivary gland induction by Scr in the trunk is limited by tsh and by Abd-B in the last abdominal segment.
Heat shock induced expression of mouse Hox genes in Drosophila embryos deficient for homeotic genes demonstrates that functional hierarchy is a universal property of the homeobox genes. Correlations exist between the expression patterns of the mouse Hox genes along the antero-posterior body axis of mice and the extent of their effect along the antero-posterior body axis of flies.
Ectopic expression of dpp eliminates Scr and Antp expression, attenuating abd-A expression, inducing Ubx, dpp, wg and tsh expression in the visceral mesoderm and inducing lab expression in the apposing endoderm. The result is failure of all of the morphogenetic events except formation of midgut constriction 2.
trx exerts its effects by positively regulating homeotic gene expression, but Ubx, Antp, abd-A, Abd-B, Scr and Dfd all have different tissue-specific, parasegment-specific and promoter-specific reductions in expression in a trx mutant background.
Antp homeodomain differs at only 5 amino acid positions from that of Scr : using ectopically expressed Antp::Scr fusion proteins, the specificity of Antp protein was shown to be determined by four specific amino acids in the flexible N-terminal arm of the homeodomain.
Scr is expressed ectopically in embryos lacking bithorax complex genes. A secondary wave of Scr activation, requiring Antp, is triggered during germ band retraction by en. This is repressed by the bithorax complex genes in the meso- and metathoracic and the abdominal segments.
The homologs of Antp, ftz, Scr, Dfd, Ama, bcd, zen, pb and lab, but not zen2 are all present in D.pseudoobscura.pseudoobscura, in the same linear order and similarly spaced along the chromosome as in D.melanogaster.
Comparative analysis of the homeobox sequences reveals the subdivision of the Antp-type homeobox genes into three classes early in metazoan evolution, one includes Abd-B, the second includes abd-A, Ubx, Antp, Scr, Dfd and ftz, and the third includes zen, zen2, pb and lab.
The N terminus of the homeodomain is critical for determining the specific effects of the Antp and Scr homeotic proteins in vivo, though other parts of the protein do have a role. The N terminal part of the homeodomain has been observed, in crystal structures and in NMR studies in solution, to contact the minor groove of the DNA.
Different homeotic genes have specific local effects on Dfd expression.
The PNS has been studied in embryos homozygous for Scr with antibodies that label specific sensory organs. The effect of ectopic expression of Scr was investigated on the normal development of sensory organs in the embryonic PNS.
ae expression is not modulated by Scr. Scr gene activity suppresses dorsala trunk development in the prothorax in the absence of ae gene activity. Scr is expressed ectopically in embryos deficient for tsh and Antp.
Scr derepression by Pc mutants causes second and third leg to first leg transformations. brm functions as an upstream activator of Scr expression.
Scr transcript pattern is altered in ae mutant embryos.
Scr gene expression is differentially regulated both temporally and spatially in a manner that is sensitive to the structure of the locus. Inclusion of Pc3 allele causes complete misregulation of the Scr locus in the leg and wing imaginal discs.
Scr is a complex locus with an extensive regulatory region that directs functions required for normal head and thoracic development in the embryo and adult.
The functional organization of Scr is determined by a series of in phase deletions and is compared to that of Antp. Ectopic expression of Scr is incapable of producing an antennae to leg transformation and induces abnormalities in the head, no ectopic belts of denticles and mouthparts tend to gather at the anterior rather than fail to involute.
E(z)+ activity is not required to initiate the expression patterns of Scr and Ubx but to maintain their repressed state.
Scr lesions can be defined into three categories. The first inactivate the entire locus, result in embryonic lethality and transformations of the first thoracic to second thoracic identity. The second are recessive semi-lethals that result in transformations of the first thoracic to second thoracic identity. The third are dominant gain-of-function lesions, when heterozygous exhibit an Scr phenotype.
Mutants in the shv region of dpp alter spatially localized expression of Scr, domain is extended anteriorly. Scr expression in the gastric caeca is repressed by dpp expression, caeca development is arrested leaving them short and broad.
Proper expression of Scr in the visceral mesoderm is essential for the development of the gastric caeca and the formation of the small constrictions that separate the caeca primordia from the main part of the midgut. In the visceral mesoderm Antp acts as a positive regulator of Scr expression.
Scr has been cloned and sequenced. It encodes a homeodomain-containing protein.
Expression domains of Scr have been identified in the midgut visceral mesoderm and the domain position defined with respect to parasegment boundaries.
Expression of the homeotic gene Scr in the visceral mesoderm is studied in pair-rule and gap gene mutant backgrounds.
Cell clones deficient for Pc and the BXC genes have abnormal wings and legs, Scr and en are derepressed in the absence of Pc and BXC function. By using the Pc- mutation and various BXC mutant combinations imaginal cell clones possessing different combinations of active homeotic genes have been generated. In the absence of BXC genes Pc- clones develop prothoracic patterns: Scr activity overrules Antp. Adding contributions of Ubx, abd-A and Abd-B results in thoracic or abdominal patterns.
Scr is one of the 18 loci identified in a screen for dominant modifiers of Pc and/or Antp phenotypes. Alleles of Pc, Pcl, Scm, Dll, brm, kto, Scr and trx show clear dominant enhancement or suppression of AntpScx, whereas alleles of vtd, Vha55, Su(Pc)37D, urd, mor, skd and osa do not.
The DNA sequences of the homeobox region of 11 Drosophila genes, including Scr, have been compared.
Mutants of Scr exhibit a reduction in sex comb teeth on the first leg.
Scr mutants display homeotic transformation of the labium to maxilla and prothorax to mesothorax.
Clonal analysis demonstrates that Scr is required in at least the ventral prothorax for specifying pro- as opposed to mesothoracic development. Ubx, Antp and Scr act in combinatorial fashion to specify segmental determination and have regulatory roles in controlling the selective expression of other genes.
Null mutations at the locus result in embryonic lethality. Animals die at the end of embryogenesis and show evidence of homeotic transformation in the cuticle derived from the labial and first thoracic segments. The first thorax is transformed to a second thoracic identity and the labial segment toward maxillary. This latter phenotype is seen as a duplication of the maxillary sense organs and the cirri. Deletions of the locus as well as null alleles also produce a dominant phenotype most clearly seen in males as a reduction in the number of sex-comb teeth. This reduction is indicative of a partial transformation of first leg to second, a conclusion borne out by the recovery of hypomorphic alleles of the locus which as hemizygotes allow survival to the adult stage and have no obvious effect in the embryo. These survivors show a complete transformation of ventral prothorax to mesothorax including the presence of sternopleural bristles on the propleurae; they also show an apparent transformation of the dorsal prothorax toward a mesothoracic identity. In addition to these thoracic transformations, the labial palps are transformed toward a maxillary palp morphology. All of these adult transformations can also been seen in X-ray-induced somatic clones of Scr- cells. Thus Scr activity is needed for proper segmental identity in both the embryo and adult in the anterior-most segment of the thorax and the posterior-most metamere of the head. In the absence of Scr product these two segments are transformed divergently to the identity of the next most posterior and anterior metamere respectively. The only other homeotic mutation to produce such a divergent homeosis is pb, which appears to act similarly in the adjacent maxillary and labial segments of the adult head. In addition to these loss-of-function mutations there are several gain-of-function dominant alleles. All result in a similar phenotype in adults, most clearly seen in males as the production of sex combs on the second and third thoracic legs. Additionally, strong alleles of this type (ScrW, ScrP, and ScrS) show the loss of sternopleural bristles indicative of a more complete transformation of mesothorax to prothorax. All of these dominants are associated with genomic rearrangements and with the exception of ScrS act as recessive lethals (ScrMsc, ScrT1, ScrT2, and ScrP) or semi-lethals (ScrW and ScrT3) at the locus. Examination of animals carrying these lesions at the end of embryogenesis as heterozygotes with a normal chromosome or hemizygotes reveals no evidence of the gain-of-function transformation of T2 and T3 transformed to T1, only the loss-of-function phenotypes described above. These phenotypic observations have been extended by showing that Scr protein is accumulated ectopically in the second and third leg imaginal discs in dominant gain-of-function genotypes but not in the second and third thoracic segments at any point in embryogenesis. Thus it appears that the spatial pattern of Scr expression is differentially regulated at these two times. Genetic analyses have shown that at least one difference lies in Scr imaginal expression being subject to a transvection-like effect. The gain-of-function lesions cause or allow the ectopic expression of the structural gene on the trans- rather than the cis-coupled transcription unit. This is most clearly seen in the case of ScrT1, which is broken within the transcribed portion of Scr and is therefore incapable of making a functional gene product. Scr mRNA is first detected in embryos in early gastrulae in a band of cells just posterior to the cephalic furrow. Protein is not detected at this time but later during germ-band elongation; it is found in the region of the labial lobe. Subsequently, during germ-band retraction, RNA and protein are detected in the first thoracic segment with the highest concentration at the anterior border of this segment. RNA and protein are also detected in the subesophageal region of the CNS in the labial ganglion and in mesodermal cells associated with the anterior midgut. As head involution proceeds, the Scr-expressing cells of the labial segment are carried inside where they are found associated with the pharynx and the mouthparts at the end of embryogenesis. In the third larval instar, protein is found in the prothoracic leg discs, the dorsal prothoracic discs, the labial discs and a small group of cells in the stalk of the antennal portion of the eye-antennal disc where it attaches to the mouthparts. In addition to this disc expression, Scr protein is accumulated in the subesophageal region of the CNS. This spatial pattern of expression in the epidermis is consistent with the spectrum of defects seen in Scr- animals and clones.