The Atypical Rho GTPase CHW-1 Works with SAX-3/Robo To Mediate Axon Guidance in .

During development, neuronal cells extend an axon toward their target destination in response to a cue to form a properly functioning nervous system. Rho proteins, Ras-related small GTPases that regulate cytoskeletal organization and dynamics, cell adhesion, and motility, are known to regulate axon guidance. Despite extensive knowledge about canonical Rho proteins (RhoA/Rac1/Cdc42), little is known about the () atypical Cdc42-like family members CHW-1 and CRP-1 in regards to axon pathfinding and neuronal migration. (Chp/Wrch) encodes a protein that resembles human Chp (Wrch-2/RhoV) and Wrch-1 (RhoU), and encodes for a protein that resembles TC10 and TCL. Here, we show that works redundantly with and in axon guidance. Furthermore, proper levels of expression and activity are required for proper axon guidance. When examining CHW-1 GTPase mutants, we found that the native CHW-1 protein is likely partially activated, and mutations at a conserved residue (position 12 using Ras numbering, position 18 in CHW-1) alter axon guidance and neural migration. Additionally, we showed that genetically interacts with the guidance receptor in PDE neurons. Finally, in VD/DD motor neurons, works downstream of to control axon guidance. In summary, this is the first study implicating the atypical Rho GTPases and in axon guidance. Furthermore, this is the first evidence of genetic interaction between and the guidance receptor These data suggest that is likely acting downstream and/or in parallel to in axon guidance.