Wasp, the Drosophila Wiskott-Aldrich syndrome gene homologue, is required for cell fate decisions mediated by Notch signaling

Wiskott-Aldrich syndrome proteins, encoded by the Wiskott-Aldrich syndrome gene family, bridge signal transduction pathways and the microfilament-base d cytoskeleton. Mutations in the Drosophila homologue, Wasp (Wsp), reveal a n essential requirement for this gene in implementation of cell fate decisi ons during adult end embryonic sensory organ development. Phenotypic analys is of Wsp mutant animals demonstrates a bias towards neuronal differentiati on, at the expense of other cell types, resulting from improper execution o f the program of asymmetric cell divisions which underlie sensory organ dev elopment. Generation of two similar daughter cells after division of the se nsory organ precursor cell constitutes a prominent defect in the Wsp. senso ry organ lineage. The asymmetric segregation of key elements such as Numb i s unaffected during this division, despite the misassignment of cell fates. The requirement for Wsp extends to additional cell fate decisions in linea ges of the embryonic central nervous system and mesoderm. The nature of the Wsp mutant phenotypes, coupled with genetic interaction studies, identifie s an essential role for Wsp in lineage decisions mediated by the Notch sign aling pathway.