The gene
mig-10 is required for the embryonic migration of the neurons CAN, ALM, and HSN, as well as the development of posterior excretory canals (Manser and Wood, 1990). We have also observed that
mig-10 is required for the formation or maintenance of the axons of the IL2 head sensory neurons (Burket et al., ECWM, 1998).
mig-10 has been cloned, and was found to have homology to the Grb family of cytoplasmic signal transduction proteins (Manser et al., 1997). In addition,
mig-10 contains a ras-associating (RA) domain, suggesting it may interact with genes of the ras superfamily of GTPases (Wojcik et al., 1999). The rac genes are members of the ras-related GTPases of the Rho family. They have been shown in a number of systems to be involved in axon guidance and cell migration. C. elegans contains three rac genes,
ced-10 ,
mig-2 , and
rac-2 , as well as two guanine nucleotide exchange factors (GEFs),
unc-73 and
exc-5 , which can activate rac GTPases by exchanging GTP for GDP. The three C. elegans rac genes have been shown to function somewhat redundantly in cell migration and axon pathfinding (Lundquist et al., 2001; Wu et al., 2002). To determine whether
mig-10 might interact with any of the rac pathway genes, we constructed double mutants of
mig-10 with the three rac and two GEF genes. We are analyzing both excretory canal development and the locations of CAN, ALM, and HSN in these mutants. Preliminary results suggest that double mutant phenotypes are more severe than those of single mutants for most of the double mutants we have constructed, suggesting that partially redundant pathways are being affected. One interpretation of these results is that
mig-10 , like
unc-73 , may interact with all three rac genes. SWT was partially supported by a WPI summer fellowship. EFR is supported by NSF CAREER Award IBN-9984662.