sis-b, sisB, T4, Hw, EG:198A6.1
Supported by strand-specific RNA-Seq data.
Gene model reviewed during 5.51
There is only one protein coding transcript and one polypeptide associated with this gene
42 (kD observed); 39 (kD predicted)
Efficient DNA binding requires dimerization with another bHLH protein. Interacts with da (via bHLH motif). Interacts with Bap60.
Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\sc using the Feature Mapper tool.
The expression of sc transcripts in the wing disc is dynamic. During the last 24hrs of the third larval instar stage, sc transcripts are expressed in the notum anlage in groups of cells that correspond to presumptive sensilla precursor regions except for that of the ventral sensillum of the third vein (L3-v).
sc transcripts are abundant during the first half of embryonic development. They reappear at lower levels in third instar larval and pupal stages. In early embryos, sc transcripts are seen in somatic nuclei but not in the yolk nuclei. They are associated with the nuclei in embryonic cycles 9 and 10, become uniformly distributed in cycle 11, peak in cycle 12, and then rapidly decay. Subsequently, the proneural expression pattern develops.
The pattern of sc expression was compared to that of ac in neurogenic region prior to the segregation of neuroblasts. The patterns are indistinguishable but the level of sc RNA is lower. The patterns of expression of ac and sc at later stages in the dorsal and lateral ectoderm are also the same.
Weak homogeneous expression is observed in the notum anlage of late third instar larvae.
ac trancripts are expressed in clusters of cells in the wing imaginal disc. The locations of the clusters coincides well with the pattern of sensory organ precursors. sc transcripts are also expressed in developing trachea.
sc transcripts are observed in the early gastrula in a striped pattern (one stripe per metamere) in the presumptive neurectoderm. Between stages 8 and 9, the pattern changes to two stripes per metamere. Later sc is expressed in the segregating neuroblasts but not in the cells that remain ectodermal. sc expression declines in neuroblasts at stage 9 as they start dividing. This pattern repeats itself as additional cells in the ectodermal layer express sc. Expression continues in cells that become neuroblasts and shuts off in cells that remain ectodermal. sc transcripts are also observed in cephalic neuroblasts and in the posterior midgut.
ac and sc transcripts are detected in a dynamic pattern from blastoderm (sc) or gastrula (ac) through stage 11 embryos. They are present in clusters of cells on the ectoderm and internally near the mesoderm. They are expressed in most neurogenic regions. Their expression patterns are very similar except in stage 9 where sc is barely detectable and ac is expressed in four longitudinal rows of clusters.
The level of unmodified sc transcripts in acHw-1, scHw-Ua, and acHw-BS third instar larvae and pupae is the same as in Oregon R. The level of sc transcripts is reduced in acHw-1+R1 revertants but is not significantly changed in acHw-1+R3 and acHw-1+R5 revertants. sc transcript levels are unchanged in su(Hw)2/su(Hw)7 heterozygotes stocks.
sc protein is first detected at nuclear cycle6 to 7 and is predominantly cytoplasmic. By nuclear cycle 10, the level of sc antilbody staining increases substantially and protein is detected in the nuclei. Nuclear sc protein increases during cycles 11-13 but some sc protein is still detected in the cytolplasm.
Expression in procephalic neuroblasts stage 9-11: deuterocerebrum - d13; protocerebrum - ad1, ad3-7, ad10, ad16, cd3, cd20, cd21, cv7, pd1, pd11, pd15-17
sc protein is first detected in 0-1 hr embryos. Protein levels increase between 1 and 3 hours and reach a peak in 3-4 hr embryos. In contrast to transcript levels, the high protein levels are maintained until the end of embryogenesis. sc protein is observed in 1st and 2nd instar larvae in contrast to sc transcripts. Protein levels increase in third instar larvae and pupae and in contrast to the transcripts are maintained into adulthood. In early embryos, two populations are observed with respect to FBgn0004170:sc protein levels. Weakly stained embryos are male embryos and darker embryos are female embryos as shown by assays for FBgn0264270:Sxl @ protein. The differences persist until the onset of gastrulation.
sc protein expression in third instar wing discs shows a dynamic pattern. In the notum anlage, sc protein is expressed initially in a number of cells greater than that expected for the number of bristles. Later the number of cells in which protein persists appears to coincide with the number of bristles. sc protein staining fades out by the end of the third instar period. Expression in the different precursors does not occur concomitantly in the wing disc.
sc protein first appears shortly before gastrulation and is present in longitudinal stripes. The highest levels are found at the border between the ventral neurogenic region and the mesoderm anlage. Expression is observed in the proneural clusters of the CNS in early germ band retraction. sc protein expression then becomes restricted to the neuroblasts that delaminate from the ectoderm. The expression in the surrounding cells of the proneural cluster decreases dramatically. Starting in stage 9, sc protein is expressed in proneural clusters of the PNS. It is first found in the proneural cluster for the P cell and then becomes restricted to the P cell. Slightly later, it is expressed in an anteriorly located proneural cluster and then is restricted to the neuronal precursor from this cluster, the A cell. It is expressed in a number of other proneural clusters and neuronal precursors until stage 11/12. At about that time expression is observed in the stomatogastric nervous system and in a subset of cells in the hindgut. Low levels of sc protein are found in sensory organs at stage 14. After stage 14, sc protein is no longer detected.
Expression of ac and sc in ectopic sensilla of h and acHw* mutants was followed with antibody staining. The pattern of expression of ac and sc prefigures the pattern of both ectopic and normal sensilla.
sc protein is localized within the nuclei of proneural clusters. Clusters grow in number and intensity of staining until the sensory organ mother cell (SMC) becomes discernable due to its more intensely stained nucleus. The sc protein disappears shortly before the SMC undergoes its first differential division. The pattern and timing of expression in specific clusters is discussed. sc protein levels are increased in emc11/emcE12 wing discs but the pattern is similar to wild type.
sc protein expression occurs in clusters of cells from which SMCs will arise. It is transiently expressed in the SMCs, often at greater levels than the surrounding cells of the proneural cluster, but not in their progeny. In ac mutants, sc protein expression is missing in the notal cells that give rise to ac-dependent machrochaetes. In emc mutants, ectopic sc protein expression occurs in single cells of the notum that will give rise to ectopic sensory organs. The acHw-49c mutation causes overexpression of sc protein.
GBrowse - Visual display of RNA-Seq signalsView Dmel\sc in GBrowse 2
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: sc CG3827
pnr directly activates the proneural ac and sc genes by binding to the enhancers responsible for their expression in the dorsocentral proneural cluster. wg has only a permissive role on dorsocentral ac-sc expression.
The sc enhancer promotes sc protein accumulation in the SMCs. Several conserved motifs are essential for its action, some of them binding sites for proneural proteins. The enhancer mediates sc self-stimulation, although only in the presence of additional factors. Cells neighboring the SMC do not acquire the neural fate because N signalling pathway effectors, the HLH proteins of the E(spl) complex, block this regulation loop.
E(spl) proteins normally mediate lateral inhibition by directly repressing proneural gene expression.
Sequence comparison between sc and Dsub\sc shows a highly conserved bHLH domain, outside this domain amino acid replacements are not randomly distributed. Two additional conserved domains, of 20 and 36 amino acids, are present near the C-terminus.
The bHLH domains of the gene products encoded by the E(spl)-C and the achaete-scute complex differ in their ability to form homo- and/or heterodimers.
The interactions established through the bHLH link the products of the E(spl)-C and the achaete-scute complexes in a single interaction network which may function to ensure that a given cell retains the capacity to choose between epidermoblast and neuroblast fates until the cell becomes definitively determined.
Proneural and neurogenic genes control specification and morphogenesis of stomatogastric nerve cell precursors.
All proneural proteins are similarly able to promote the segregation of a neural precursor at the MP2 neuroblast position but show distinct capacities in its specification.
Loss of function mutations in the achaete-scute complex lead to a significant reduction in sensory bristles and glial cells. Neurogenesis and gliogenesis share the same genetic pathway, though the mechanism of action of the the achaete-scute complex is different in the two processes.
Overexpression of da, but not the ectopic expression of the achaete-scute complex genes l(1)sc or sc, leads to the formation of ectopic neural cells in embryonic tissue without neural competence. This effect is strongly enhanced by coexpressing l(1)sc or sc.
The highly complex pattern of proneural clusters is constructed piecemeal by the action of site-specific enhancer like elements on ac and sc. These elements are distributed along most of the AS-C. The cross-activation between ac and sc does not occur detectably between the endogenous ac and sc genes in most proneural clusters. Coexpression is accomplished by activation of both ac and sc by the same set of position-specific enhancers.
da/sc heterodimers directly activate the Sxl early promoter by binding to both high and low affinity sites. dpn protein represses this activation by specific binding to a unique site within the Sxl early promoter.
The yeast two hybrid system has been used to demonstrate specific interactions within the sisA, sc, dpn and da group of gene products, and to delimit their interaction domains. The results support and extend the model of the molecular basis of the X/A ratio signal.
When daughters lack her function a duplication of sc can improve prospects but be made worse by a single mutation of sisA. Males with extra wild type sisA or sc genes have an increased chance of survival when maternal her function is defective.
ac-sc complex genes are expressed in neuronal precursor cells, so expressed ventrally in insects and vertebrate homologs are expressed dorsally. This situation is thought to have evolved due to an inversion of the dorsoventral axis. The inversion occurred during early chordate evolution, the chordates turned upside down and henceforth were carrying the nerve cord on their dorsal side.
emc forms heterodimers with the ac, sc, l(1)sc, and da products. emc inhibits DNA-binding of ac, sc and l(1)sc/da heterodimers and da homodimers. emc is a repressor of sc function whose action may take place post-transcriptionally.
Mutants associated with lesions in the zinc finger domain of pnr show overexpression of ac and sc and the development of extra neural precursors. Mutations in the putative amphipathic helices of pnr act as hyperactive repressor molecules causing a loss of ac and sc expression and a loss of neural precursors.
The specific combination of the achaete-scute complex genes expressed at one site does not play a role in defining the fate of the progenitor cell that is formed at that site. Individual sense organs depend mostly or exclusively on one of the achaete-scute complex genes because the cis-regulatory sites active at the corresponding location act mostly or exclusively on that particular gene.
In the embryo, ac and sc are expressed coincidentally, at reproducible anterior-posterior and dorso-ventral coordinates, in clusters from which neuroblasts will arise. The AP and DV position is regulated through a common regulatory element between ac and sc that is under the control of pair rule, segment polarity and DV patterning genes.
Direct, positive transcriptional autoregulation by the ac protein and cross-regulation by sc are essential for high level expression of the ac promoter in the proneural cluster. These auto- and cross-regulatory activities are antagonized in a dose-dependent manner by the emc gene product.
In vitro DNA binding assays using gel retardation to an ac promoter region and hb zygotic promoter region target sequence demonstrates that da protein elicits a weak homodimeric binding and da/ac or da/sc heterodimers bind tightly.
The sis-b function of sc interacts with the genes Sxl, da and sisA to initiate the female mode of development. sc is required in all regions of the embryo to activate Sxl, run cooperates with sc to activate Sxl in the central region.
The sis-b+ function, whose dosage is pivotal to the communication of the X:A ratio in sex determination, is conferred by the T4 protein encoded by sc.
The regulatory regions of the 'sis-b' function, which controls sc expression in sex determination, are both separable from and simpler than those of the 'scα' function, which controls sc expression in neurogenesis.
Expression of sc stimulates expression of ac, and vice versa, therefore removal of one gene leads to the absence of both proneural gene products and sensory organs in the sites specified by it cis-regulatory sequences.
DNA sequence analysis reveals four E box binding sites, for the binding of hetero-oligomeric complexes composed of da or AS-C proteins, in the first 877 bp of the ac upstream region. Electrophoretic mobility shift assays demonstrate that the emc protein can specifically antagonise DNA binding of the da/AS-C complexes in vitro in a dose-dependent manner, h and E(spl) proteins fail to exhibit this inhibitory effect.
Absence of the achaete-scute complex genes causes neuroectodermal cells to enter the epidermal pathway of development.
The capacity for primordia to respond to sc is temporally and spatially regulated. Neither ac nor sc is required to specify the type of sense organ and the sense organ position utilises topological information independent of ac and sc gene products.
Loss-of-function mutants cause loss of specific clusters of bristles, while gain-of-function mutants cause the appearance of ectopic bristles.
Analysis of flies deficient for the sc and/or ac genes shows that the complete pattern of campaniform sensilla on the wing results from the superimposition of two independent subpatterns, one of which depends on sc, the other on ac.
Many sensilla precursors of the dorsal radius require sc activity to reach differentiation.
The achaete-scute complex defines the basic topology of the sense organ pattern, rather than the type or precise location of the elements. The achaete-scute complex is an essential component of es and nd neuron development.
The achaete-scute complex plays a role in determination and early differentiation of embryonic neural cells.
The interactions between h, emc and the ASC are studied to determine their relationships. The results indicate that h and emc code for repressors that interact with the ac and sc region of the ASC respectively.
The density of chaetae in emc1/emc2 flies with different doses of sc+ show a saturation effect on the notum, wing and tergite. The spatial distribution of the chaetae results from cell interactions probably by a mechanism of lateral inhibition.
sc rearrangements with breakpoints in the 'scα' region have their second breakpoints in pericentric heterochromatin, whereas those broken in the 'scβ' region have euchromatic second breakpoints.
Numerous sc alleles have been described, the great majority of which are associated either with chromosome rearrangements with one breakpoint in region 1B or with inserts of foreign DNA. Nearly all chromosomal lesions with sc effects map proximal to the presumptive sc transcription unit; two inversions with breakpoints just distal to the transcription unit have slight effects; proximal lesions map to either side of l(1)sc and strength of expression is inversely correlated with the molecular distance between the lesion and the scute transcription unit. Proceeding from right to left, lesions remove bristles from the mesonotum in a roughly hierarchical fashion in the following order: scutellars, (postverticals, ocellars, sternopleurals, anterior and medial orbitals, postalars), anterior notopleurals, (posterior orbitals, postverticals, anterior supra-alars) (presuturals, orbitals), with those enclosed in parentheses tending to be removed together (see Ghysen and Dambly-Chaudiere, 1988). Transcription first observed in early gastrula in regions with neurogenic potential, but before any overt evidence of neurogenesis apparent. As development proceeds, a complex temporal and spatial program of expression, mostly in neurogenic precursor cells ensues; expression ceases during the period of germ band shortening (Cabrera, Martinez-Arias and Bate, 1987) (Romani, Campuzano and Modolell, 1987). In third instar larvae, expression in wing discs is confined to restricted subsets of cells known to correspond to regions giving rise to precursors of cuticular sense organs that are under control of sc (Romani, Campuzano, Macagno and Modolell, 1989).
Specifies the differentiation of numerous macrochaetae on the head and thorax as well as microchaetae on the tergites: anterior, medial and posterior orbital, posterior vertical, ocellar and postvertical bristles on the head plus humeral, presutural, anterior and posterior notopleural, anterior supra-alar, sternopleural, anterior and posterior postalar and anterior and posterior scutellar bristles on the mesothorax; also participates with ac in specifying the anterior vertical, posterior supra-alar and anterior dorsocentral bristles; specifies the majority of the campaniform sensilla on the wing blade (Leyns, Dambly-Chaudiere and Ghysen, 1989). Males deficient for sc, e.g., In(1)sc8Lsc4R, are poorly viable and catatonic; homozygous deficient females lethal; males deficient for both ac and sc, e.g., In(1)y3PLsc4R, are lethal (Garcia-Bellido, 1979). sc deficiencies suppress the phenotype of emc; extra doses of ASC enhance the emc phenotype (del Prado and Garcia-Bellido, 1984). Alleles of the Hw series are gain of function alleles of the achaete-scute complex, which lead to the development of supernumerary bristles and hairs in all segments of the fly: in the prefrons, postfrons, postgena and occipital regions of the head; in the preepisternum, episternum, anepisternum, scutum, scutellum, postnotum, wingblade, legs, humerus and halteres of the thorax; and in the tergites, pleura and sternites of the abdomen. Phenotype suppressed by three doses of h+ (Botas, del Prado and Garcia-Bellido, 1982) and enhanced by h, emc and pyd (Neel, 1941; del Prado and Garcia-Bellido, 1984). Numbers of super numerary bristles reduced in da+ hemizygotes (Dambly-Chaudiere, Ghysen, Jan and Jan, 1988).