Gene Symbol: da
Description: daughterless
Alias: 5102, CG5102, Dmel\CG5102, SC_DA, bHLHb22, l(2)31Ea, l(2)k08611, daughterless, CG5102-PA, CG5102-PB, CG5102-PC, da-PA, da-PB, da-PC, daughter-less, lethal (2) k08611
Species: fruit fly

Top Publications

  1. Caudy M, Grell E, Dambly Chaudiere C, Ghysen A, Jan L, Jan Y. The maternal sex determination gene daughterless has zygotic activity necessary for the formation of peripheral neurons in Drosophila. Genes Dev. 1988;2:843-52 pubmed
    The daughterless (da) gene is known to have separate maternal and zygotic functions: Maternally supplied daughterless activity is required for proper sex determination and dosage compensation in female embryos, whereas loss of zygotically ..
  2. Wong M, Castanon I, Baylies M. Daughterless dictates Twist activity in a context-dependent manner during somatic myogenesis. Dev Biol. 2008;317:417-29 pubmed publisher
    ..by its dimerization partner: Twi homodimers activate genes necessary for somatic myogenesis, whereas Twi/Daughterless (Da) heterodimers lead to the repression of these genes...
  3. Bailey A, Posakony J. Suppressor of hairless directly activates transcription of enhancer of split complex genes in response to Notch receptor activity. Genes Dev. 1995;9:2609-22 pubmed
    ..Our results establish Su(H) as a direct regulatory link between N receptor activity and the expression of E(spl)-C genes, extending the known linear structure of the N cell-cell signaling pathway. ..
  4. Li X, Cassidy J, Reinke C, Fischboeck S, Carthew R. A microRNA imparts robustness against environmental fluctuation during development. Cell. 2009;137:273-82 pubmed publisher
    ..We suggest that some conserved microRNAs like miR-7 may enter into novel genetic relationships to buffer developmental programs against variation and impart robustness to diverse regulatory networks. ..
  5. Murre C, McCaw P, Baltimore D. A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell. 1989;56:777-83 pubmed
    ..Both cDNAs share a region of extensive identity to the Drosophila daughterless gene and obvious similarity to a segment in three myc proteins, MyoD, and members of the Drosophila achaete-..
  6. Paroush Z, Finley R, Kidd T, Wainwright S, Ingham P, Brent R, et al. Groucho is required for Drosophila neurogenesis, segmentation, and sex determination and interacts directly with hairy-related bHLH proteins. Cell. 1994;79:805-15 pubmed
  7. Quan X, Denayer T, Yan J, Jafar Nejad H, Philippi A, Lichtarge O, et al. Evolution of neural precursor selection: functional divergence of proneural proteins. Development. 2004;131:1679-89 pubmed
    ..These data suggest an evolutionary divergence in the mechanisms of NPC selection between protostomes and deuterostomes. ..
  8. González A, Lu H, Erickson J. A shared enhancer controls a temporal switch between promoters during Drosophila primary sex determination. Proc Natl Acad Sci U S A. 2008;105:18436-41 pubmed publisher
    ..Activation of SxlPm depends on the scute, daughterless, and runt transcription factors, which communicate X chromosome dose to SxlPe, but is independent of the X ..
  9. Murre C, McCaw P, Vaessin H, Caudy M, Jan L, Jan Y, et al. Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell. 1989;58:537-44 pubmed
    ..The HLH domain can mediate heterodimer formation between either daughterless, E12, or E47 (Class A) and achaete-scute T3 or MyoD (Class B) to form proteins with high affinity for the kappa ..

More Information


  1. Sukhanova M, Deb D, Gordon G, Matakatsu M, Du W. Proneural basic helix-loop-helix proteins and epidermal growth factor receptor signaling coordinately regulate cell type specification and cdk inhibitor expression during development. Mol Cell Biol. 2007;27:2987-96 pubmed
    ..transcription factor Pointed (Pnt) and the proneural basic helix-loop-helix proteins Atonal (Ato) and Daughterless (Da)...
  2. Cadigan K, Jou A, Nusse R. Wingless blocks bristle formation and morphogenetic furrow progression in the eye through repression of Daughterless. Development. 2002;129:3393-402 pubmed
    ..that wingless mediates both effects, at least in part, through repression of the basic helix-loop-helix protein Daughterless. daughterless is required for high proneural gene expression and furrow progression...
  3. Caudy M, Vässin H, Brand M, Tuma R, Jan L, Jan Y. daughterless, a Drosophila gene essential for both neurogenesis and sex determination, has sequence similarities to myc and the achaete-scute complex. Cell. 1988;55:1061-7 pubmed
    b>daughterless (da) has multiple functions in Drosophila embryonic development: maternal da activity is necessary for proper sex determination, and zygotic da activity is necessary for formation of the peripheral nervous system...
  4. Keyes L, Cline T, Schedl P. The primary sex determination signal of Drosophila acts at the level of transcription. Cell. 1992;68:933-43 pubmed
    ..The proteins produced from these early mRNAs then initiate the autoregulatory loop by directing the female-specific processing of transcripts from the late Sxl promoter. ..
  5. Campos Ortega J, Knust E. Molecular analysis of a cellular decision during embryonic development of Drosophila melanogaster: epidermogenesis or neurogenesis. Eur J Biochem. 1990;190:1-10 pubmed
    ..thought to lead to neural development through the participation of the genes of the achaete-scute complex and daughterless, which are members of a family of DNA-binding regulatory proteins and of the gene vnd whose molecular nature is ..
  6. Giagtzoglou N, Koumbanakis K, Fullard J, Zarifi I, Delidakis C. Role of the Sc C terminus in transcriptional activation and E(spl) repressor recruitment. J Biol Chem. 2005;280:1299-305 pubmed
    ..In vivo, the Sc C-terminal domain is required for E(spl) recruitment in an enhancer context-dependent fashion, suggesting that in some enhancers alternative interaction surfaces can be used to recruit E(spl) proteins. ..
  7. Baonza A, de Celis J, Garcia Bellido A. Relationships between extramacrochaetae and Notch signalling in Drosophila wing development. Development. 2000;127:2383-93 pubmed
    ..We propose that at least during vein differentiation and wing margin formation, extramacrochaetae is regulated by Notch and collaborates with other Notch-downstream genes such as Enhancer of split-m(beta). ..
  8. González Crespo S, Levine M. Interactions between dorsal and helix-loop-helix proteins initiate the differentiation of the embryonic mesoderm and neuroectoderm in Drosophila. Genes Dev. 1993;7:1703-13 pubmed
    ..HLH proteins that have been implicated previously in sex determination and neurogenesis (daughterless, achaete, and scute) are shown to be required for the formation of these embryonic tissues...
  9. Bhattacharya A, Baker N. The HLH protein Extramacrochaetae is required for R7 cell and cone cell fates in the Drosophila eye. Dev Biol. 2009;327:288-300 pubmed publisher
    ..A model is proposed in which Extramacrochaetae acts in parallel to or as a feed-forward regulator of the E(spl)-Complex to promote Notch signaling in particular cellular contexts. ..
  10. Alifragis P, Poortinga G, Parkhurst S, Delidakis C. A network of interacting transcriptional regulators involved in Drosophila neural fate specification revealed by the yeast two-hybrid system. Proc Natl Acad Sci U S A. 1997;94:13099-104 pubmed
    ..fidelity of the system was established by its ability to closely reproduce the already documented interactions among Da, Ac, Sc, and Extramacrochaetae...
  11. Campuzano S. Emc, a negative HLH regulator with multiple functions in Drosophila development. Oncogene. 2001;20:8299-307 pubmed
    ..However, while maintaining this repressive molecular mechanism, emc also appears to act as a positive regulator of differentiation...
  12. MacArthur S, Li X, Li J, Brown J, Chu H, Zeng L, et al. Developmental roles of 21 Drosophila transcription factors are determined by quantitative differences in binding to an overlapping set of thousands of genomic regions. Genome Biol. 2009;10:R80 pubmed publisher
  13. Castanon I, Von Stetina S, Kass J, Baylies M. Dimerization partners determine the activity of the Twist bHLH protein during Drosophila mesoderm development. Development. 2001;128:3145-59 pubmed
    ..We find that Twist can form homodimers and heterodimers with the Drosophila E protein homologue, Daughterless, in vitro...
  14. Ik Tsen Heng J, Tan S. The role of class I HLH genes in neural development--have they been overlooked?. Bioessays. 2003;25:709-16 pubmed
    ..This essay supports this possibility, in addition to putting forward the hypothesis that, outside their general dimerisation activity, class I genes have independent roles in regulating neurogenesis. ..
  15. Brown N, Paddock S, Sattler C, Cronmiller C, Thomas B, Carroll S. daughterless is required for Drosophila photoreceptor cell determination, eye morphogenesis, and cell cycle progression. Dev Biol. 1996;179:65-78 pubmed
    ..encode basic helix-loop-helix (bHLH) transcription factors that dimerize in vitro with another bHLH protein, daughterless (da)...
  16. Tanaka Matakatsu M, Miller J, Borger D, Tang W, Du W. Daughterless homodimer synergizes with Eyeless to induce Atonal expression and retinal neuron differentiation. Dev Biol. 2014;392:256-65 pubmed publisher
    ..In this manuscript, we show that a linked dimer of Daughterless (Da), the only Drosophila class I bHLH protein, activates Atonal (Ato) expression and retinal neuron ..
  17. Jarman A, Grau Y, Jan L, Jan Y. atonal is a proneural gene that directs chordotonal organ formation in the Drosophila peripheral nervous system. Cell. 1993;73:1307-21 pubmed
    ..Like the ASC products, ato protein contains a basic-helix-loop-helix region and heterodimerizes with daughterless protein to bind to E boxes. Moreover, ectopic expression of ato promotes the formation of extra sense organs...
  18. Bhattacharya A, Baker N. A network of broadly expressed HLH genes regulates tissue-specific cell fates. Cell. 2011;147:881-92 pubmed publisher
    ..In Drosophila, a cross-interacting regulatory network links expression of the E protein Daughterless (Da), which heterodimerizes with bHLH proteins to activate them, with expression of the Id protein ..
  19. Cabrera C, Alonso M. Transcriptional activation by heterodimers of the achaete-scute and daughterless gene products of Drosophila. EMBO J. 1991;10:2965-73 pubmed
    The achaete-scute complex (AS-C) and the daughterless (da) genes encode helix-loop-helix proteins which have been shown to interact in vivo and to be required for neurogenesis...
  20. Zarifi I, Kiparaki M, Koumbanakis K, Giagtzoglou N, Zacharioudaki E, Alexiadis A, et al. Essential roles of Da transactivation domains in neurogenesis and in E(spl)-mediated repression. Mol Cell Biol. 2012;32:4534-48 pubmed publisher
    ..b>Daughterless (Da) is the sole E protein in Drosophila and is ubiquitously expressed...
  21. Cronmiller C, Schedl P, Cline T. Molecular characterization of daughterless, a Drosophila sex determination gene with multiple roles in development. Genes Dev. 1988;2:1666-76 pubmed
    The daughterless (da) gene in Drosophila acts both maternally and zygotically to provide essential functions during development...
  22. Kux K, Kiparaki M, Delidakis C. The two Tribolium E(spl) genes show evolutionarily conserved expression and function during embryonic neurogenesis. Mech Dev. 2013;130:207-25 pubmed publisher
    ..A number of other activities have been evolutionarily conserved, most notably their ability to interact with proneural proteins Scute and Daughterless.
  23. Cronmiller C, Cummings C. The daughterless gene product in Drosophila is a nuclear protein that is broadly expressed throughout the organism during development. Mech Dev. 1993;42:159-69 pubmed
    The daughterless (da) gene in Drosophila functions in the regulation of at least three significant developmental pathways: sex determination, neurogenesis and oogenesis...
  24. Bopp D, Bell L, Cline T, Schedl P. Developmental distribution of female-specific Sex-lethal proteins in Drosophila melanogaster. Genes Dev. 1991;5:403-15 pubmed
    ..We also show that Sxl expression in the early embryo is sex specific and depends on maternal daughterless and zygotic sisterless-b activity in accordance with the established roles of these genes as positive ..
  25. Giagtzoglou N, Alifragis P, Koumbanakis K, Delidakis C. Two modes of recruitment of E(spl) repressors onto target genes. Development. 2003;130:259-70 pubmed
    ..Irrespective of whether E(spl) are recruited via direct DNA binding or interaction with proneural proteins, the co-repressor Groucho is always needed for target gene repression. ..
  26. Kaspar M, Schneider M, Chia W, Klein T. Klumpfuss is involved in the determination of sensory organ precursors in Drosophila. Dev Biol. 2008;324:177-91 pubmed publisher
    ..We present a detailed structure function analysis that identifies functionally important domains within Klu. ..
  27. Jafar Nejad H, Tien A, Acar M, Bellen H. Senseless and Daughterless confer neuronal identity to epithelial cells in the Drosophila wing margin. Development. 2006;133:1683-92 pubmed
    The basic helix-loop-helix (bHLH) proneural proteins Achaete and Scute cooperate with the class I bHLH protein Daughterless to specify the precursors of most sensory bristles in Drosophila...
  28. Cronmiller C, Cline T. The Drosophila sex determination gene daughterless has different functions in the germ line versus the soma. Cell. 1987;48:479-87 pubmed
    As a regulator of the female-specific gene Sxl, da+ provides an essential maternal component in the control of sex determination and dosage compensation; nevertheless, neither the maternal nor zygotic phenotypes of the original mutant da ..
  29. Garrell J, Modolell J. The Drosophila extramacrochaetae locus, an antagonist of proneural genes that, like these genes, encodes a helix-loop-helix protein. Cell. 1990;61:39-48 pubmed
    ..These and other findings suggest the existence of a network of synergistic and antagonistic interactions, mediated by HLH proteins, that participates in the establishment of the neural fate. ..
  30. zur Lage P, Powell L, Prentice D, McLaughlin P, Jarman A. EGF receptor signaling triggers recruitment of Drosophila sense organ precursors by stimulating proneural gene autoregulation. Dev Cell. 2004;7:687-96 pubmed publisher
    ..This exemplifies a simple and general mechanism for regulating the transition from competence to cell fate commitment whereby a cell signal directly targets the autoregulation of a selector gene...
  31. Brand M, Jarman A, Jan L, Jan Y. asense is a Drosophila neural precursor gene and is capable of initiating sense organ formation. Development. 1993;119:1-17 pubmed
    ..In both cases, this process requires daughterless and the proneural genes achaete, scute and lethal-of-scute of the achaete-scute complex...
  32. Chang P, Hsiao Y, Tien A, Li Y, Pi H. Negative-feedback regulation of proneural proteins controls the timing of neural precursor division. Development. 2008;135:3021-30 pubmed publisher
    ..As phyl is a direct transcriptional target of Ac and Sc, our data suggest that, in addition to mediating cell cycle arrest, proneural protein initiates a negative-feedback regulation to time the mitotic entry of neural precursors...
  33. Wainwright S, Ish Horowicz D. Point mutations in the Drosophila hairy gene demonstrate in vivo requirements for basic, helix-loop-helix, and WRPW domains. Mol Cell Biol. 1992;12:2475-83 pubmed
    ..We show that the h protein in Drosophila virilis closely resembles that in D. melanogaster and includes completely conserved bHLH and WRPW domains...
  34. Nolo R, Abbott L, Bellen H. Senseless, a Zn finger transcription factor, is necessary and sufficient for sensory organ development in Drosophila. Cell. 2000;102:349-62 pubmed
    ..Sens is then in turn required to further activate and maintain proneural gene expression. This feedback mechanism is essential for selective enhancement and maintenance of proneural gene expression in the SOPs. ..
  35. Van Doren M, Ellis H, Posakony J. The Drosophila extramacrochaetae protein antagonizes sequence-specific DNA binding by daughterless/achaete-scute protein complexes. Development. 1991;113:245-55 pubmed
    ..Proteins encoded by the daughterless (da) gene and three genes of the achaete-scute complex (AS-C) act positively in the determination of the ..
  36. Vaessin H, Brand M, Jan L, Jan Y. daughterless is essential for neuronal precursor differentiation but not for initiation of neuronal precursor formation in Drosophila embryo. Development. 1994;120:935-45 pubmed
    ..the proneural genes of the achaete-scute complex AS-C (achaete (ac), scute (sc) and lethal of scute (l'sc)) and daughterless (da). The da protein dimerizes with AS-C products in vitro to form DNA-binding proteins...
  37. Yasugi T, Umetsu D, Murakami S, Sato M, Tabata T. Drosophila optic lobe neuroblasts triggered by a wave of proneural gene expression that is negatively regulated by JAK/STAT. Development. 2008;135:1471-80 pubmed publisher
  38. Hinz U, Giebel B, Campos Ortega J. The basic-helix-loop-helix domain of Drosophila lethal of scute protein is sufficient for proneural function and activates neurogenic genes. Cell. 1994;76:77-87 pubmed
    ..Finally, the bHLH domain is necessary and sufficient to mediate the proneural function, to activate neurogenic genes, and to allow lateral inhibition. ..
  39. Jarman A, Brand M, Jan L, Jan Y. The regulation and function of the helix-loop-helix gene, asense, in Drosophila neural precursors. Development. 1993;119:19-29 pubmed
    ..We show that this element contains binding sites for AS-C/daughterless heterodimers...
  40. Fisher A, Caudy M. The function of hairy-related bHLH repressor proteins in cell fate decisions. Bioessays. 1998;20:298-306 pubmed
    ..This general function in cell fate specification has been conserved from Drosophila to vertebrates and has implications for human disease pathogenesis. ..
  41. Castanon I, Baylies M. A Twist in fate: evolutionary comparison of Twist structure and function. Gene. 2002;287:11-22 pubmed
    ..Conserved principles and the molecular mechanisms underlying them are discussed. ..
  42. Fisher A, Ohsako S, Caudy M. The WRPW motif of the hairy-related basic helix-loop-helix repressor proteins acts as a 4-amino-acid transcription repression and protein-protein interaction domain. Mol Cell Biol. 1996;16:2670-7 pubmed
    ..These results directly demonstrate that Groucho family proteins are active transcriptional corepressors for Hairy-related proteins and are recruited by the 4-amino acid protein-protein interaction domain, WRPW. ..
  43. Singson A, Leviten M, Bang A, Hua X, Posakony J. Direct downstream targets of proneural activators in the imaginal disc include genes involved in lateral inhibitory signaling. Genes Dev. 1994;8:2058-71 pubmed
    ..Thus, one of the earliest steps in adult peripheral neurogenesis is the direct activation by proneural proteins of genes involved in restricting the expression of the SOP cell fate. ..
  44. Van Doren M, Powell P, Pasternak D, Singson A, Posakony J. Spatial regulation of proneural gene activity: auto- and cross-activation of achaete is antagonized by extramacrochaetae. Genes Dev. 1992;6:2592-605 pubmed
    ..Our results indicate that emc plays an essential early role in defining territories of bristle-forming potential. ..
  45. Cronmiller C, Cline T. The relationship of relative gene dose to the complex phenotype of the daughterless locus in Drosophila. Dev Genet. 1986;7:205-21 pubmed
    The daughterless (da) gene provides an essential maternally supplied component for Drosophila sex determination and dosage compensation...
  46. Rusch J, Levine M. Threshold responses to the dorsal regulatory gradient and the subdivision of primary tissue territories in the Drosophila embryo. Curr Opin Genet Dev. 1996;6:416-23 pubmed
  47. Simpson P, Bourouis M, Heitzler P, Ruel L, Haenlin M, Ramain P. Delta, notch, and shaggy: elements of a lateral signaling pathway in Drosophila. Cold Spring Harb Symp Quant Biol. 1992;57:391-400 pubmed
  48. Johnson E, Wayne S, Nagoshi R. fs (1) Yb is required for ovary follicle cell differentiation in Drosophila melanogaster and has genetic interactions with the Notch group of neurogenic genes. Genetics. 1995;140:207-17 pubmed
    ..1) Yb alleles also interact with genes that are known to act with or regulate Notch activity, including Delta, daughterless, and mastermind...
  49. Rosay P, Colas J, Maroteaux L. Dual organisation of the Drosophila neuropeptide receptor NKD gene promoter. Mech Dev. 1995;51:329-39 pubmed
    ..In addition, we show that the proneural protein atonal, in association with daughterless, transactivates the NKD promoter in Schneider S2 cells via the proximal E box NKDE2...
  50. Held L. Bristle patterning in Drosophila. Bioessays. 1991;13:633-40 pubmed
    ..Some of the genes that control these events participate in more than one stage, and others play key roles in seemingly unrelated developmental pathways, including embryonic neurogenesis, body segmentation, and sex determination. ..
  51. Steinmann Zwicky M. How do germ cells choose their sex? Drosophila as a paradigm. Bioessays. 1992;14:513-8 pubmed
    ..Some of the genes that are involved in germ line sex determination have been identified. In other species, including vertebrates, inductive signals are commonly used to determine the sex of germ cells. ..
  52. Nagel A, Preiss A. Notchspl is deficient for inductive processes in the eye, and E(spl)D enhances split by interfering with proneural activity. Dev Biol. 1999;208:406-15 pubmed
    ..Nspl is the first Notch mutation known to specifically affect Notch inductive processes during eye development. ..
  53. Wildonger J, Mann R. Evidence that nervy, the Drosophila homolog of ETO/MTG8, promotes mechanosensory organ development by enhancing Notch signaling. Dev Biol. 2005;286:507-20 pubmed
    ..Nvy is specifically expressed in the SOP, where it interacts with the Ac and Sc DNA binding partner Daughterless (Da) and affects the expression of Ac and Sc targets...
  54. Mackay T. The genetic basis of quantitative variation: numbers of sensory bristles of Drosophila melanogaster as a model system. Trends Genet. 1995;11:464-70 pubmed
    ..The consensus emerging from the application of all approaches is that much of the mutational and segregating variation affecting bristle number is attributable to alleles with large phenotype effects at a small number of candidate loci. ..
  55. Miklos G. Molecules and cognition: the latterday lessons of levels, language, and lac. Evolutionary overview of brain structure and function in some vertebrates and invertebrates. J Neurobiol. 1993;24:842-90 pubmed
    ..Finally, I analyze the concepts of "perceptual categorization" and "information processing" and the difficulties involved in the extrapolation of computer analogies to sophisticated nervous systems. ..
  56. Bate M, Rushton E, Currie D. Cells with persistent twist expression are the embryonic precursors of adult muscles in Drosophila. Development. 1991;113:79-89 pubmed
    ..The distribution of these cells is tightly linked to the pattern of peripheral nerves, but they segregate normally in da/da embryos despite the absence of the peripheral nervous system.
  57. Duffy J, Gergen J. The Drosophila segmentation gene runt acts as a position-specific numerator element necessary for the uniform expression of the sex-determining gene Sex-lethal. Genes Dev. 1991;5:2176-87 pubmed
  58. Kyriacou C. Clock research perring along: it's about time!. Trends Genet. 1994;10:69-71 pubmed
  59. King Jones K, Korge G, Lehmann M. The helix-loop-helix proteins dAP-4 and daughterless bind both in vitro and in vivo to SEBP3 sites required for transcriptional activation of the Drosophila gene Sgs-4. J Mol Biol. 1999;291:71-82 pubmed
    ..As a second component of SEBP3 we identified the Daughterless (Da) protein, which is also ubiquitously expressed and binds to SEBP3 sites independent of dAP-4...
  60. Tsuda H, Jafar Nejad H, Patel A, Sun Y, Chen H, Rose M, et al. The AXH domain of Ataxin-1 mediates neurodegeneration through its interaction with Gfi-1/Senseless proteins. Cell. 2005;122:633-44 pubmed
    ..Interestingly, loss of Gfi-1 mimics SCA1 phenotypes in Purkinje cells. These results indicate that the Atx-1/Gfi-1 interaction contributes to the selective Purkinje cell degeneration in SCA1. ..
  61. Lee K, Kim S, Kim E, Ha E, You H, Kim B, et al. Bacterial-derived uracil as a modulator of mucosal immunity and gut-microbe homeostasis in Drosophila. Cell. 2013;153:797-811 pubmed publisher
    ..These results reveal that bacteria with distinct abilities to activate uracil-induced gut inflammation, in terms of intensity and duration, act as critical factors that determine homeostasis or pathogenesis in gut-microbe interactions. ..