title: The IMD innate immunity pathway of Drosophila influences somatic sex determination via regulation of the Doa locus.
abstract: The IMD pathway induces the innate immune response to infection by gram-negative bacteria. We demonstrate strong female-to-male sex transformations in double mutants of the IMD pathway in combination with Doa alleles. Doa encodes a protein kinase playing a central role in somatic sex determination through its regulation of alternative splicing of dsx transcripts. Transcripts encoding two specific Doa isoforms are reduced in Rel null mutant females, supporting our genetic observations. A role for the IMD pathway in somatic sex determination is further supported by the induction of female-to-male sex transformations by Dredd mutations in sensitized genetic backgrounds. In contrast, mutations in either dorsal or Dif, the two other NF-κB paralogues of Drosophila, display no effects on sex determination, demonstrating the specificity of IMD signaling. Our results reveal a novel role for the innate immune IMD signaling pathway in the regulation of somatic sex determination in addition to its role in response to microbial infection, demonstrating its effects on alternative splicing through induction of a crucial protein kinase.
authors.affiliation: Université Paris Sud, UMR8195, Bâtiment 442 bis, 91405 Orsay Cedex, France.
authors.forename: Yunpo
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Université Paris Sud, UMR8195, Bâtiment 442 bis, 91405 Orsay Cedex, France.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cocco
authors.affiliation: Université Paris Sud, UMR8195, Bâtiment 442 bis, 91405 Orsay Cedex, France.
authors.forename: Severine
authors.initials: S
authors.lastname: Domenichini
authors.affiliation: Université Paris Sud, UMR8195, Bâtiment 442 bis, 91405 Orsay Cedex, France.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Samson
authors.affiliation: Université Paris Sud, UMR8195, Bâtiment 442 bis, 91405 Orsay Cedex, France. Electronic address: Leonard.Rabinow@u-psud.fr.
authors.forename: Leonard
authors.initials: L
authors.lastname: Rabinow
mesh_terms: D000483:Alleles; D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000276:immunology* / Q000648:ultrastructure; D004843:Epistasis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D017344:Genes, Insect; D056426:Genetic Loci; D006579:Heterozygote; D007113:Immunity, Innate / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D019849:Sex Determination Processes / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D029721:Drosophila Proteins; D016328:NF-kappa B; D020033:Protein Isoforms; C089977:Doa protein, Drosophila; D017346:Protein Serine-Threonine Kinases
keywords: DOA kinase; Drosophila; IMD pathway; NF-κB; Sex determination