Gene Symbol: sisA
Description: sisterless A
Alias: CG1641, DM29, Dmel\CG1641, sis A, sis a, sis-A, sis-a, sisa, sisterless A, CG1641-PA, sisA-PA, sisterlessA
Species: fruit fly
Products:     sisA

Top Publications

  1. Barbash D, Cline T. Genetic and molecular analysis of the autosomal component of the primary sex determination signal of Drosophila melanogaster. Genetics. 1995;141:1451-71 pubmed
    ..X:A signal by selecting for dominant suppressors of a female-specific lethal mutation in the numerator element, sisterlessA (sisA). Ten suppressors were recovered in this extensive genome-wide selection...
  2. Pomiankowski A, Nöthiger R, Wilkins A. The evolution of the Drosophila sex-determination pathway. Genetics. 2004;166:1761-73 pubmed
    ..Our hypothesis is built on the available data from Drosophila and other insect species, and we point out where it is amenable to further experimental and comparative tests. ..
  3. Erickson J, Cline T. A bZIP protein, sisterless-a, collaborates with bHLH transcription factors early in Drosophila development to determine sex. Genes Dev. 1993;7:1688-702 pubmed
  4. Cline T, Meyer B. Vive la différence: males vs females in flies vs worms. Annu Rev Genet. 1996;30:637-702 pubmed
    ..Although no overlap has been found among the molecules used by flies and worms to achieve sex determination, striking similarities have been found in the genetic strategies used by these two species to differentiate their sexes. ..
  5. ten Bosch J, Benavides J, Cline T. The TAGteam DNA motif controls the timing of Drosophila pre-blastoderm transcription. Development. 2006;133:1967-77 pubmed publisher
  6. Younger Shepherd S, Vaessin H, Bier E, Jan L, Jan Y. deadpan, an essential pan-neural gene encoding an HLH protein, acts as a denominator in Drosophila sex determination. Cell. 1992;70:911-22 pubmed
  7. Mar n I, Baker B. The evolutionary dynamics of sex determination. Science. 1998;281:1990-4 pubmed
  8. Gempe T, Beye M. Function and evolution of sex determination mechanisms, genes and pathways in insects. Bioessays. 2011;33:52-60 pubmed publisher
    ..This review summarises recent findings in insects, surveys evidence of how and why sex determination mechanisms can change rapidly and suggests fruitful areas of future research. ..
  9. Zeidler M, Bach E, Perrimon N. The roles of the Drosophila JAK/STAT pathway. Oncogene. 2000;19:2598-606 pubmed publisher
    ..Oncogene (2000)...

More Information


  1. McKeown M. Sex determination and differentiation. Dev Genet. 1994;15:201-4 pubmed
  2. Louis M, Holm L, Sanchez L, Kaufman M. A theoretical model for the regulation of Sex-lethal, a gene that controls sex determination and dosage compensation in Drosophila melanogaster. Genetics. 2003;165:1355-84 pubmed
    ..Numerical simulations of mutant genotypes enable us to reproduce and explain the phenotypic effects of perturbations induced in the dosage of genes whose products participate in the early Sxl promoter activation. ..
  3. Cline T. A female-specific lethal lesion in an X-linked positive regulator of the Drosophila sex determination gene, Sex-lethal. Genetics. 1986;113:641-63 pubmed
  4. Kappes G, Deshpande G, Mulvey B, Horabin J, Schedl P. The Drosophila Myc gene, diminutive, is a positive regulator of the Sex-lethal establishment promoter, Sxl-Pe. Proc Natl Acad Sci U S A. 2011;108:1543-8 pubmed publisher
    ..Here we show that the Drosophila Myc gene diminutive is an X-linked numerator. ..
  5. Zeidler M, Perrimon N. Sex determination: co-opted signals determine gender. Curr Biol. 2000;10:R682-4 pubmed
    ..Recent results have identified Unpaired as an activator of sex-lethal and revealed a new role for the JAK-STAT pathway in sex determination. ..
  6. Nothiger R, Steinmann Zwicky M. Genetics of sex determination: what can we learn from Drosophila?. Development. 1987;101 Suppl:17-24 pubmed
  7. Steinmann Zwicky M. Sex determination in Drosophila: the X-chromosomal gene liz is required for Sxl activity. EMBO J. 1988;7:3889-98 pubmed
    ..This shows that SxlM1 is not truly expressed constitutively in animals with an X:A ratio of 0.5, but requires activity of liz for initiation or maintenance. ..
  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
    ..transcription factors, which communicate X chromosome dose to SxlPe, but is independent of the X signal element sisA and the maternal co-repressor groucho...
  9. Bartolomé C, Maside X, Yi S, Grant A, Charlesworth B. Patterns of selection on synonymous and nonsynonymous variants in Drosophila miranda. Genetics. 2005;169:1495-507 pubmed
    ..The joint intensity of selection and biased gene conversion, in terms of the product of effective population size and the sum of the selection and conversion coefficients, was estimated to be approximately 0.65. ..
  10. Pultz M, Baker B. The dual role of hermaphrodite in the Drosophila sex determination regulatory hierarchy. Development. 1995;121:99-111 pubmed
    ..We conclude that the maternal and zygotic functions of her are needed at two distinctly different levels of the sex determination regulatory hierarchy. ..
  11. Sanchez L, Granadino B, Torres M. Sex determination in Drosophila melanogaster: X-linked genes involved in the initial step of sex-lethal activation. Dev Genet. 1994;15:251-64 pubmed
    ..We review these data and present new data on two more regions of the X chromosome that define other genes needed for Sxl activation. In addition, we report on the interaction between some of the genes regulating Sxl activation. ..
  12. Oliver B, Pauli D, Mahowald A. Genetic evidence that the ovo locus is involved in Drosophila germ line sex determination. Genetics. 1990;125:535-50 pubmed
    ..The ovo locus appears to be involved in germ line sex determination and is linked in some manner to sex determination in the soma. ..
  13. Granadino B, Santamaria P, Sanchez L. Sex determination in the germ line of Drosophila melanogaster: activation of the gene Sex-lethal. Development. 1993;118:813-6 pubmed
    ..We conclude that the somatic component of the gonads in Sxlf7M1/Sxlfc females is affected, and consequently germ cells do not develop.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  14. Garrell J, Campuzano S. The helix-loop-helix domain: a common motif for bristles, muscles and sex. Bioessays. 1991;13:493-8 pubmed
    ..These structural properties provide a molecular mechanism to explain the synergistic and antagonistic functional relations among the HLH encoding genes that control several developmental pathways. ..
  15. Botella L, Doñoro C, Sanchez L, Segarra C, Granadino B. Cloning and characterization of the scute (sc) gene of Drosophila subobscura. Genetics. 1996;144:1043-51 pubmed
    ..The D. subobscura Sc protein can cooperate with other D. melanogaster bHLH proteins because D. subobscura sc supplies sis-b function when introduced into D. melanogaster transgenic flies mutant for sc. ..
  16. Torres M, Sanchez L. The sisterless-b function of the Drosophila gene scute is restricted to the stage when the X:A ratio determines the activity of Sex-lethal. Development. 1991;113:715-22 pubmed
    ..Finally, we have analyzed, by in situ hybridization, the effect of sc and sis-a mutations on the embryonic transcription of Sxl. Our results support the view that the control of Sxl by the X:A signal occurs at the transcriptional level. ..
  17. Cline T, Dorsett M, Sun S, Harrison M, Dines J, Sefton L, et al. Evolution of the Drosophila feminizing switch gene Sex-lethal. Genetics. 2010;186:1321-36 pubmed publisher
    ..The potential evolutionary relevance of these nonessential functions is discussed...
  18. Jan Y, Jan L. Functional gene cassettes in development. Proc Natl Acad Sci U S A. 1993;90:8305-7 pubmed
  19. Parkhurst S, Meneely P. Sex determination and dosage compensation: lessons from flies and worms. Science. 1994;264:924-32 pubmed
    ..Instead, the study of sex determination and dosage compensation is providing more general lessons about different types of signaling pathways used to control alternative developmental states of cells and organisms. ..
  20. Liu Y, Belote J. Protein-protein interactions among components of the Drosophila primary sex determination signal. Mol Gen Genet. 1995;248:182-9 pubmed
    ..These results support and extend the model of the molecular basis of the X/A ratio signal. ..
  21. Moller A, Avila F, Erickson J, Jackle H. Drosophila BAP60 is an essential component of the Brahma complex, required for gene activation and repression. J Mol Biol. 2005;352:329-37 pubmed
    ..binds DNA and shows genetic and physical interactions with the sex-determining transcription factors encoded by sisterless A and scute...
  22. Gladstein N, McKeon M, Horabin J. Requirement of male-specific dosage compensation in Drosophila females--implications of early X chromosome gene expression. PLoS Genet. 2010;6:e1001041 pubmed publisher
    ..Our data suggest that before the female state is set, the ground state is male and female X chromosome expression is elevated. Females thus utilize the male dosage compensation process to amplify the signal which determines their fate. ..
  23. Farrell J, O Farrell P. From egg to gastrula: how the cell cycle is remodeled during the Drosophila mid-blastula transition. Annu Rev Genet. 2014;48:269-94 pubmed publisher
    ..Finally, we consider how the elements of this program may be conserved or changed in other organisms. ..
  24. Granadino B, Torres M, Bachiller D, Torroja E, Barbero J, Sanchez L. Genetic and molecular analysis of new female-specific lethal mutations at the gene Sxl of Drosophila melanogaster. Genetics. 1991;129:371-83 pubmed
  25. Moussian B, Söding J, Schwarz H, NUSSLEIN VOLHARD C. Retroactive, a membrane-anchored extracellular protein related to vertebrate snake neurotoxin-like proteins, is required for cuticle organization in the larva of Drosophila melanogaster. Dev Dyn. 2005;233:1056-63 pubmed
    ..We propose that this binding function of Rtv may assist the organization of chitin fibers at the epidermal cell surface during cuticle assembly. ..
  26. Salz H, Flickinger T. Both loss-of-function and gain-of-function mutations in snf define a role for snRNP proteins in regulating Sex-lethal pre-mRNA splicing in Drosophila development. Genetics. 1996;144:95-108 pubmed
    ..Based on these studies we suggest a model in which the snRNP protein, Snf, functions with Sex-lethal to block recognition of the regulated male-specific exon. ..
  27. Erickson J. Primary Sex Determination in Drosophila melanogaster Does Not Rely on the Male-Specific Lethal Complex. Genetics. 2016;202:541-9 pubmed publisher included female-lethal genetic interactions between the seven msl genes and either Sxl or scute and sisterlessA, two of the X-signal elements (XSE) that regulate early Sxl expression...
  28. Erickson J, Cline T. Key aspects of the primary sex determination mechanism are conserved across the genus Drosophila. Development. 1998;125:3259-68 pubmed
    In D. melanogaster, a set of 'X:A numerator genes', which includes sisterlessA (sisA), determines sex by controlling the transcription of Sex-lethal (Sxl). We characterized sisA from D. pseudoobscura and D...
  29. Jinks T, Polydorides A, Calhoun G, Schedl P. The JAK/STAT signaling pathway is required for the initial choice of sexual identity in Drosophila melanogaster. Mol Cell. 2000;5:581-7 pubmed
    ..upd also functions as a numerator element in regulating wild-type Sxl-Pe reporters. We demonstrate that the JAK kinase, Hopscotch, and the STAT DNA-binding protein, Marelle, are also required for Sxl-Pe activation. ..
  30. McKeown M, Madigan S. Sex determination and differentiation in invertebrates: Drosophila and Caenorhabditis elegans. Curr Opin Cell Biol. 1992;4:948-54 pubmed
    ..We are now gaining an understanding of the molecular mechanisms governing the largely post-transcriptional regulation of the intermediate steps in these cascades. ..
  31. Sarpal R, Todi S, Sivan Loukianova E, Shirolikar S, Subramanian N, Raff E, et al. Drosophila KAP interacts with the kinesin II motor subunit KLP64D to assemble chordotonal sensory cilia, but not sperm tails. Curr Biol. 2003;13:1687-96 pubmed
    ..However, the flagellar assembly in Drosophila spermatids does not require Kinesin II and is independent of IFT. ..
  32. Smith J, Cronmiller C. The Drosophila daughterless gene autoregulates and is controlled by both positive and negative cis regulation. Development. 2001;128:4705-14 pubmed
    ..Our analysis of da(lyh) identifies it as the first springer insertion that functions as an insulating element, with its disruptive activity mediated by the product of a fourth chromosome gene, Suppressor of lyh [Su(lyh)]. ..
  33. Parkhurst S, Lipshitz H, Ish Horowicz D. achaete-scute feminizing activities and Drosophila sex determination. Development. 1993;117:737-49 pubmed
    ..Detailed examination of Sxl expression in rescued embryos suggests that female cells may be viable in the absence of detectable Sxl protein expression. ..
  34. Erickson J, Cline T. Molecular nature of the Drosophila sex determination signal and its link to neurogenesis. Science. 1991;251:1071-4 pubmed
    ..In this model there is no need to invoke the existence of analogous autosomal negative regulators of Sex-lethal. ..
  35. 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. ..
  36. Walker J, Lee K, Desai R, Erickson J. The Drosophila melanogaster sex determination gene sisA is required in yolk nuclei for midgut formation. Genetics. 2000;155:191-202 pubmed
    During sex determination, the sisterlessA (sisA) gene functions as one of four X:A numerator elements that set the alternative male or female regulatory states of the switch gene Sex-lethal...
  37. Estes P, Keyes L, Schedl P. Multiple response elements in the Sex-lethal early promoter ensure its female-specific expression pattern. Mol Cell Biol. 1995;15:904-17 pubmed
    ..Conversely, maintaining the promoter silent in males requires the repressive activities of denominator genes, and at least one of the denominator genes also appears to function through target sequences within the promoter. ..
  38. Jinks T, Calhoun G, Schedl P. Functional conservation of the sex-lethal sex determining promoter, Sxl-Pe, in Drosophila virilis. Dev Genes Evol. 2003;213:155-65 pubmed publisher
    ..These findings suggest that low-affinity target sites for the X/A counting system are critical for the functioning of Sxl-Pe...
  39. Hodgkin J. Sex determination compared in Drosophila and Caenorhabditis. Nature. 1990;344:721-8 pubmed
    ..In contrast, the underlying molecular mechanisms appear to be very different in these two species. Developmental processes such as sex determination need not be strongly conserved in evolution. ..
  40. Leatherman J, Levin L, Boero J, Jongens T. germ cell-less acts to repress transcription during the establishment of the Drosophila germ cell lineage. Curr Biol. 2002;12:1681-5 pubmed
  41. Pauli D, Mahowald A. Germ-line sex determination in Drosophila melanogaster. Trends Genet. 1990;6:259-64 pubmed
    ..Only some of the genes involved in somatic sex determination are also needed for germ cell development. Recent genetic studies have identified loci required for germ-line sex determination. ..
  42. Sefton L, Timmer J, Zhang Y, Beranger F, Cline T. An extracellular activator of the Drosophila JAK/STAT pathway is a sex-determination signal element. Nature. 2000;405:970-3 pubmed
    ..Unlike sex signals for other organisms, sisC has acquired its sex-specific function while maintaining non-sex-specific roles in development, a characteristic that it shares with all other Drosophila XSEs. ..
  43. Parkhurst S, Bopp D, Ish Horowicz D. X:A ratio, the primary sex-determining signal in Drosophila, is transduced by helix-loop-helix proteins. Cell. 1990;63:1179-91 pubmed
    ..We propose that X chromosomes are counted through heterodimers of helix-loop-helix transcription factors that act synergistically to initiate Sxl expression. ..
  44. Cline T. Evidence that sisterless-a and sisterless-b are two of several discrete "numerator elements" of the X/A sex determination signal in Drosophila that switch Sxl between two alternative stable expression states. Genetics. 1988;119:829-62 pubmed
    ..In that same study it was concluded that region 3E8-4F11 of the X chromosome contained especially potent X/A numerator elements.(ABSTRACT TRUNCATED AT 400 WORDS) ..
  45. Marx J. Tracing how the sexes develop. Science. 1995;269:1822-4 pubmed
  46. Bernstein M, Lersch R, Subrahmanyan L, Cline T. Transposon insertions causing constitutive Sex-lethal activity in Drosophila melanogaster affect Sxl sex-specific transcript splicing. Genetics. 1995;139:631-48 pubmed
  47. Pritchard D, Schubiger G. Activation of transcription in Drosophila embryos is a gradual process mediated by the nucleocytoplasmic ratio. Genes Dev. 1996;10:1131-42 pubmed
  48. 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. ..
  49. Wrischnik L, Timmer J, Megna L, Cline T. Recruitment of the proneural gene scute to the Drosophila sex-determination pathway. Genetics. 2003;165:2007-27 pubmed
    ..The screen that yielded new sc alleles also generated autosomal duplications that argue against the textbook view that fruit fly sex signal evolution recruited a set of autosomal signal elements comparable to the XSEs...
  50. 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...