title: Recruitment of the proneural gene scute to the Drosophila sex-determination pathway.
abstract: In flies, scute (sc) works with its paralogs in the achaete-scute-complex (ASC) to direct neuronal development. However, in the family Drosophilidae, sc also acquired a role in the primary event of sex determination, X chromosome counting, by becoming an X chromosome signal element (XSE)-an evolutionary step shown here to have occurred after sc diverged from its closest paralog, achaete (ac). Two temperature-sensitive alleles, sc(sisB2) and sc(sisB3), which disrupt only sex determination, were recovered in a powerful F1 genetic selection and used to investigate how sc was recruited to the sex-determination pathway. sc(sisB2) revealed 3' nontranscribed regulatory sequences likely to be involved. The sc(sisB2) lesion abolished XSE activity when combined with mutations engineered in a sequence upstream of all XSEs. In contrast, changes in Sc protein sequence seem not to have been important for recruitment. The observation that the other new allele, sc(sisB3), eliminates the C-terminal half of Sc without affecting neurogenesis and that sc(sisB1), the most XSE-specific allele previously available, is a nonsense mutant, would seem to suggest the opposite, but we show that housefly Sc can substitute for fruit fly Sc in sex determination, despite lacking Drosophilidae-specific conserved residues in its C-terminal half. Lack of synergistic lethality among mutations in sc, twist, and dorsal argue against a proposed role for sc in mesoderm formation that had seemed potentially relevant to sex-pathway recruitment. 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.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3204, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Wrischnik
authors.forename: John R
authors.initials: JR
authors.lastname: Timmer
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Megna
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Cline
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D005075:Biological Evolution; D018389:Codon, Nonsense; D004268:DNA-Binding Proteins / Q000235:genetics*; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005804:Genes, Lethal; D008297:Male; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009474:Neurons / Q000502:physiology*; D010641:Phenotype; D012045:Regulatory Sequences, Nucleic Acid; D012641:Selection, Genetic; D019849:Sex Determination Processes; D015398:Signal Transduction; D013696:Temperature; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D019076:Transgenes; D014960:X Chromosome / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D014157:Transcription Factors; C089197:sc protein, Drosophila