FB2021_06, released December 14, 2021
Gene: Dmel\da
Gene: Dmel\da
Please see the JBrowse view of Dmel\da for information on other features
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Low-frequency RNA-Seq exon junction(s) not annotated.
Gene model reviewed during 5.45
Stop-codon suppression (UAG) postulated; FBrf0234051.
Gene model reviewed during 6.25
3.4, 3.2, 2.954 (longest cDNA)
82 (kD observed); 74 (kD predicted)
710 (aa); 74 (kD predicted)
Homodimer. Efficient DNA binding requires dimerization with another bHLH protein. Interacts with Amos. Interacts (via bHLH motif) with sisA and sc. Interacts with dpn (via bHLH motif).
Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\da using the Feature Mapper tool.
Comment: maternally deposited
There are two phases of da expression during oogenesis. In the first phase, da transcripts are detected throughout the germarium and in all egg chambers in both germ line and the somatic cells until approximately stage S3. After stage S3, transcripts are not detected in the germ line and are detected at low levels in the follicle cells. The late expression phase starts in stage S8 at which point strong expression is observed in the germ line in the nurse cells and increases until late stage 10. At that point transfer of da transcripts to the oocyte is initiated. Weak expression continues to be observed in follicle cells.
Both da transcripts are present at constant proportion in all stages of development. The 3.2 kb transcript is slightly overrepresented in 0-2.5 hr embryos (in comparison to other developmental stages).
da is expressed in cells of the intestinal stem cell lineage in adult posterior midgut.
da protein expression is first seen as a dorsoventral stripe, several cells wide, at the anterior side of the morphogenetic furrow that quickly resolves into expression in single cells within the 2-3 ommatidial rows in the posterior portion of the furrow. The single da-expressing cells appear to be R8 cells. da protein expression exactly corresponds with ato protein expression.
da protein is widely distributed throughout the somatic component of the ovary. Expression is first observed in prefollicular cells and follicle cells from germarium region 2 until stage S3. The most intense staining is seen at the anterior portion of the germarium at stage 3 as a nascent follicle is ready to pinch off from the germarium. In egg chambers through stage S3, da protein expression is maintained in all the nuclei of follicular epithelial cells. Protein levels diminish in the follicular epithelium thereafter. Throughout egg chamber maturation, expression is observed in interfollicular stalk cells and interfollicular polar cells. In stage S9 and beyond, uniform levels of da protein are observed in all follicle cells.
da protein is observed in the nuclei of most cells during embryogenesis but is not present in pole cells. da protein is present throughout the preblastoderm embryo and disappears before blastoderm formation. Protein levels increase again before germ band extension and reach maximal levels during stages 9-11. da protein is present in ectodermal cells as well as in putative neuroblasts during the process of neuroblast delamination and after. The levels of da protein are fairly uniform across the ectodermal layer. Neuronal precursors, however, appear to have elevated levels of da protein. da protein expression is reduced in most tissue types during germ band retraction. At later stages higher levels of da protein are seen n particular tissues including a subset of CNS cells, salivary glands, and parts of the gut and muscles. In wing imagingal discs, a uniform level of da protein is observed in all epidermal cells. An elevated protein level is observed in some neuronal precursor cells. In leg discs, elevated da protein levels are seen in the large cluster of SOPS that will later form the chordotonal organ. In eye discs, elevated da protein levels are seen in cells posterior to the morphogenetic furrow that are thought to correspond to R8 cells.
da protein is detected at all developmental stages on western blots. Peak levels are observed in 5-12hr embryos. da protein was found to be expressed continuously and ubiquitously during embryogenesis by immunolocalization. In later stages, protein levels are highest in the supraoesophageal ganglion, the ventral cord and the salivary gland. The only nuclei that appear not to contain da protein are the vitellophages. In larvae, the highest levels of da protein are observed in the imaginal discs (eye-antenna, wing, leg, haltere, and labial), in salivary glands, and in a subset of cells in the CNS. During oogenesis, da protein is detected in follicle cells but not in the germline. Finally, da protein is detected in male gona s. In the testis, light staining is observed in apically located cells and heavy staining is observed in somatic cyst cells and in terminal epithelial cells. Intense staining is also observed in the seminal vescicle and the anterior ejaculatory duct epithelia.
GBrowse - Visual display of RNA-Seq signals
View Dmel\da in GBrowse 2Please 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.
monoclonal
polyclonal
Source for merge of: da l(2)k08611
DNA-protein interactions: genome-wide binding profile assayed for da protein in 2-3 hr embryos; see BDTNP1_TFBS_da collection report.
Analysis of the function of da.
Four genes whose products are required for various stages of the cell cycle are misexpressed in the PNS of da mutant embryos.
da is autonomously required for the neurogenesis of all photoreceptor cells that differentiate within the furrow. Both da and ato are independently activated within the eye disc, proper maintenance of both da and ato expression is dependent on the other protein. Loss of da disrupts the progression of the morphogenetic furrow and this effect is mediated by the loss of both hh and dpp. Also da function is necessary for reentry into the cell cycle by cells of the second mitotic wave posterior to the morphogenetic furrow.
Proneural and neurogenic genes control specification and morphogenesis of stomatogastric nerve cell precursors.
Overexpression of da using the GAL4 system, but not the ectopic expression of the AS-C genes l(1)sc or sc, leads to the formation of ectopic neural cells in embryonic tissue without neural competence. This effect os strongly enhanced by coexpressing l(1)sc or sc. Expression of da and/or l(1)sc is not sufficient to overcome the lateral inhibition in the analgen of the embryonic nervous system.
da is required for the survival of salivary gland cells after they invaginate.
Proneural gene products (ac, da and l(1)sc) activate transcription of Dl in the neuroectoderm by binding to specific sites within its promoter. This transcriptional activation enhances lateral inhibition and helps ensure that cells in the vicinity of prospective neuroblasts will themselves become epidermoblasts.
A fragment of the D.melanogaster da gene has been used as a probe for in situ hybridisation of Chrysomya rufifacies polytene chromosomes.
da is not required for the initial appearance of nascent neuronal precursors but is required for these cells to express multiple neuronal precursor genes and to produce the normal number of neurons.
Ten (unnamed) recessive lethal alleles have been isolated during a cytogenetic analysis of chromosomal region 31.
da encodes a nuclear protein that is widely expressed throughout development.
dpn expression in da mutant embryos has been examined: all neural precursors are abnormal, do not express dpn and produce very few neurons. Later in development dpn is found in some CNS neurons.
Mutations at da, hup and dal loci have no effect on position-effect variegation. Mutant alleles are sensitive to amounts of heterochromatin in the genome.
In cotransfection studies the highest levels of ac expression are achieved when a combination of ac and da or sc expression vectors are present in the cotransfection mixture.
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. Single copy yeast promoters under the control of the GAL4 promoter were used to test whether ac, sc and da proteins could activate transcription of a Ecol\lacZ reporter gene in the yeast assay system. da produces slight activation and the presence of da gives strong activation of the reporter gene. Results suggest that da/l(1)sc heterodimers can function as transcriptional activators in direct proportion to their DNA-binding affinities.
sisA gene product acts in combination with maternally encoded products of signal transduction genes, da, which communicate the number of X chromosomes to Sxl and thereby determine sexual fate.
da is required in all regions of the embryo to activate Sxl.
Mutations in maternal class gene da interact with RpII140wimp.
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.
da alleles act as enhancers of spl alleles of N.
The da gene product may be capable of functionally complementing the genes of ASC.
E12 and E47 binding factors bind to the murine immunoglobulin kappa chain enhancer. These cDNAs show sequence similarity with da.
Defects in neural development caused by mutations in da can be prevented by the presence of mutations in N, bib, mam, neu, Dl amd E(spl).
Double hemizygotes for the achaete-scute complex and da <up>Df(1)260-1/+; Df(2L)J27/+</up> or the achaete-scute complex and Df(4)M101-62f show loss of macrochaetae, which none of the single hemizygotes does.
Duplications carrying wild type and mutant da alleles have been used to determine the relationship between maternal and zygotic activities of the da locus and whether zygotic functions of da are important in the control of Sxl sex determination activities. Individuals with three doses of da+ show no decrease in viability or fertility. Increasing the maternal and zygotic da+ dose reduces the severity of the recessive lethal effect of mutant da alleles and reducing the maternal da+ dose reduces female lethal maternal effect of mutant da alleles. da+ zygotic function is not involved in Sxl+ regulation: lowered da+ zygotic dose does not reduce Sxl+ expression of sex determination functions.
da+ performs multiple roles during development. Maternally supplied da+ is required in female embryos as a positive activator of the gene, Sex-lethal (Sxl), the key binary switch gene for the sex determination pathway. Also, da+ expression is required in the somatic gonad of adult females for proper egg membrane formation and hence for the survival of all progeny regardless of their sex. Embryonic expression of da+ is required in both sexes for the formation of the peripheral nervous system (PNS) and parts of the central nervous system (CNS). And, during larval and/or pupal stages, da+ may be required for the growth and/or differentiation of cells that form the adult cuticle. Amorphic alleles (da2, da3, da5, etc.) are recessive lethals, with a lethal period which is predominantly embryonic (Cronmiller and Cline, 1987; Caudy et al., 1988). In addition, the hypomorphic allele, da1 (originally called da), is hemizygous (da1/da deficiencies) lethal (Mange and Sandler, 1973), and da1 homozygotes die when they undergo the first half of embryonic development at 29oC (Cline, 1976). Death appears to be a consequence of dosage compensation defects (Cline, 1983a; Gergen, 1987). Viability of da1 homozygotes is improved by the presence of extra X or Y heterochromatin in either the parental female or her progeny (Sandler, 1972; Mason, 1973). Temperature-sensitive lethality of the da1 zygotic lethal effect is not affected by the Sxl genotype (Cline, 1980). da+ is not required in the germ-line, since da- (da2/da3) pole cells produce fertile gametes; however, mitotic recombination failed to yield significant da- (da2 or da3) somatic clones, suggesting da+ may be essential during epidermal development (Cronmiller and Cline, 1987). Embryos, homozygous for lethal da alleles, have a reduced CNS, lack all peripheral neurons and have no external sensory structures (Caudy et al., 1988). Adult flies heterozygous for a deletion of the achaete-scute (ASC) genes and simultaneously heterozygous for Df(da) (also da2/+ or da5/+) exhibit characteristic bristle defects (Dambly-Chaudiere, Ghysen, Jan and Jan 1988). Hemizygosity for da+ reduces the number of supernumerary bristles in Hw mutants (Dambly-Chaudiere, Ghysen, Jan and Jan, 1988). In addition to its zygotic phenotype, da1 exhibits two separable maternal effects. There is a female-specific maternal effect: At 22oC and 25oC, homozygous da1 females produce no daughters, while at 18oC, they produce approximately 20% as many daughters as sons (Cline, 1976). At 29oC, da1 displays a sex-nonspecific maternal effect. Homozygous females are reversibly sterile; they lay eggs that show little or no development (Cline, 1976). Sterility of da1 females at high temperature results from a defect in the somatic gonad rather than in the germ-line, since da- germ cells in wild-type ovaries produce normal eggs which support full viability of sons (Cronmiller and Cline, 1987). The female-specific maternal effect has a temperature-sensitive period which includes the last 60 hr of oogenesis and the first 3 hr of development (Cline, 1976). This maternal effect is also observed in crosses of da1 females to D.simulans males (Watanabe and Yamada, 1977). The female-lethal maternal effect is autonomous to the germ-line, as demonstrated by transplantation of da1, or da2/da3 pole cells into + hosts (Cline, 1983b; Cronmiller and Cline, 1987). Female zygotes from da1 mothers at 25oC die as embryos. Such lethal female embryos show consistent abnormalities in midgut formation, and in about 50% of the abnormal embryos, shortening of the germ band fails, while anus and posterior spiracles open on the dorsal surface behind the head segments (Counce). Female embryos from da1 mothers also show consistent defects in the CNS, which is either reduced in width or shows abrupt bends or twists; abnormally formed gut often extends into the CNS (Caudy et al., 1988). The majority of daughters of da1 mothers surviving at 18oC are morphologically abnormal, often missing structures from one or more imaginal discs or abdominal histoblasts and frequently with duplication of structures (Cline, 1976). Though it was reported that daughters of homozygous da1 females could be rescu
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