DISTINCT MORPHOGENETIC FUNCTIONS OF SIMILAR SMALL GTPASES - DROSOPHILA DRAC1 IS INVOLVED IN AXONAL OUTGROWTH AND MYOBLAST FUSION

The small GTPases of the Rac/Rho/Cdc42 subfamily are implicated in act in cytoskeleton-membrane interaction in mammalian cells and budding ye ast. The in vivo functions of these GTPases in multicellular organisms are not known. We have cloned Drosophila homologs of rac and CDC42, D rac1, and Dcdc42. They share 70% amino acid sequence identity with eac h other, and both are highly expressed in the nervous system and mesod erm during neuronal and muscle differentiation, respectively. We expre ssed putative constitutively active and dominant-negative Drac1 protei ns in these tissues. When expressed in neurons, Drac1 mutant proteins cause axon outgrowth defects in peripheral neurons without affecting d endrites. When expressed in muscle precursors, they cause complete fai lure of, or abnormality in, myoblast fusion. Expressions of analogous mutant Dcdc42 proteins cause qualitatively distinct morphological defe cts, suggesting that similar GTPases in the same subfamily have unique roles in morphogenesis.