Characterization of putative effector proteins for the small GTPase, Cdc42, during drosophila development

The Rho subfamily GTPases (Rho, Rac, Cdc42) are small GTP-binding proteins that act as molecular switches, controlling many cellular functions. These GTPases fluctuate between a GTP-bound 'on7 state and a GDP-bound 'off state, and convey signals into the cell. Cdc42 has been implicated in a diverse array of processes, including vesicular trafficking, gene expression, formation of F-actin based membrane protrusions (filopodia), cell polarity, apoptosis, and cell cycle regulation. Model systems such as Drosophila have furthered the understanding of the hnctional roles of Cdc42 in epithelial morphogenesis, establishment of cell polarity, and neuronal path finding and development. The use of model systems allows the study of molecular processes at levels not possible in cell culture. These include genetic approaches and the study of gene function at the level of tissue morphogenesis. Three putative downstream effectors for Cdc42, originally identified in mammals, were studied in Drosophila. DCIP4, a putative cytoskeletal regulator, is expressed in a dynamic pattern throughout development. DCIP4 is required during oogenesis and functions with Cdc42 in crossvein development. The two members of the Drosophila ACK nonreceptor tyrosine kinase family, DACK and DPR2, are both expressed at the leading edge epidennis during the embryonic process of dorsal closure. DACK functions downstream of Cdc42 in dorsal closure, but is not required for JNK signalling during embryonic development. However, DACK may modulate signalling downstream of, or in parallel to, the Decapentaplegic pathway in this process.