Distinct roles of Rac GTPases and the UNC-73/Trio and PIX-1 Rac GTP exchange factors in neuroblast protrusion and migration in C. elegans.

The Rac and Cdc42 GTPases as well as the multiple GTP exchange factors that regulate their activity have been implicated in the pathways that drive actin cytoskeleton reorganization, but the individual contributions of these molecules to cell migration remain unknown. Studies shown here examine the roles of CED-10/Rac, MIG-2/RhoG and CDC-42 in the migration of the QL and QR neuroblasts in C. elegans. CED-10/Rac was found to normally limit protrusion and migration, whereas MIG-2/RhoG was required for protrusion and migration. CED-10/Rac and MIG-2/RhoG also had redundant roles in Q protrusion and migration. Surprisingly, CDC-42 was found to have only weak effects on the protrusion and the migration. We found that a mutation of unc-73/Trio, which encodes a GEF for CED-10/Rac and MIG-2/RhoG, caused protrusions that were thin and filopodia-like, suggesting that UNC-73/Trio is required for robust lamellipodia-like protrusion. A screen of the 19 C. elegans Dbl homology Rho GEF genes revealed that PIX-1 was required for proper Q neuroblast protrusion and migration. Genetic analysis indicated that PIX-1 might act in the CED-10/Rac pathway in parallel to MIG-2/RhoG and that PIX-1 has redundant function with UNC-73/Trio in Q neuroblast protrusion and migration. These results indicate that Rho GTPases and GEFs have both unique and overlapping roles in neuronal migration.