Developmental and molecular contexts for the functions of Waspand Scar,Drosophila homologs of a conserved family of cytoskeletal regulators. E.D. Schejter ¹, S. Ben-Yaacov ¹, Y. Cohen ¹, T. Tal ¹, D. Vaizel-Ohayon ¹, J.A. Zallen ^1,2. 1) Dept Molecular Genetics, Weizmann Inst Science, Rehovot, Israel; 2) Dept Molecular Biology, Princeton Univ., Princeton, NJ.

   Members of the WASP/SCAR protein family respond to various signaling molecules by promoting the microfilament-nucleating capacity of the Arp2/3 protein complex, thereby linking signal transduction pathways to cytoskeletal control over cell morphology. Our analysis of mutant alleles in Wasp(Wsp)and Scarsuggests distinct functional requirements for these single Drosophila homologs of each of the major branches of this important family of cytoskeletal elements.
   Disruption of Scarfunction results in profound effects on cell morphology in a variety of organs and cell types, at various stages of Drosophila development. Egg chamber morphology during oogenesis, structural integrity of the embryonic central nervous system, and adult eye development provide prominent examples of tissues adversely affected in Scarmutants. In contrast to the widespread requirement for Scar,Wspacts in a surprisingly narrow developmental context, namely, in the control of lineage decisions during embryonic and adult sensory organ formation. Improper execution of the program of asymmetric cell divisions, which underlies sensory organ development, leads to a predominance of neuronal differentiation at the expense of non-neuronal cell-types in Wspmutants. The nature of the Wspmutant phenotypes, coupled with genetic interaction studies, imply a role for Wspin cell-fate decisions mediated by the Notchsignaling pathway.
   Studies designed to determine the degree to which the signaling context of WASP proteins is conserved in Drosophila, suggest that a functional interaction with the Arp2/3 complex is an essential feature of Wspactivity. However, signaling via the GTPase CDC42, a key WASP effector in mammalian cells, does not appear to play a major role in Drosophila Wspfunction.