Drosophila homologs of the mammalian WASP/SCAR protein family mediate various aspects of neurogenesis. E.D. Schejter , I. Abramson , S. Ben-Yacov , Y. Cohen , T. Tal , J. Zallen. Dept Molecular Genetics, Weizmann Inst of Science, Rehovot, Israel.

   The mammalian WASP (Wiskott Aldrich Syndrome protein) and SCAR genes encode multi-domain proteins, which have been recognized as key mediators between various signal transduction pathways and the actin-based cytoskeleton. In particular, these proteins have been shown to promote microfilament formation in concert with the Arp2/3 complex, in response to various cytoplasmic signals. We have identified and characterized Drosophila homologs of both WASP and SCAR, which exhibit all the structural hallmarks of their mammalian counterparts. Lethal mutant alleles in both loci have been recovered. Flies carrying zygotic mutations in the D-WASP locus die at or soon after eclosion, and are characterized by a lack of sensory bristles on various portions of the adult cuticle. Embryos derived from D-WASP germline clones exhibit defects in development of PNS sensory organs. Our analysis suggests improper execution of asymmetric cell-divisions as the basis for the D-WASP mutant phenotypes. Strong genetic interactions with the Notch pathway have been observed, suggesting a possible role for D-WASP in Notch-based signaling. The D-SCAR mutant phenotype indicates an involvement of this gene in embryonic CNS development.