Members of the rho family of small GTPases have been implicated and characterized in a variety of cytoskeletal regulatory events. However, the spatial and temporal regulation of the activities of such proteins in vivo is not well understood and represents an important aspect of the cell movements and morphogenesis required during animal development. By expressing dominant-negative and dominant-active versions of the C. elegans rhoA homologue
rho-1 from a tissue specific promoter (
col-10), we establish a role for
rho-1 during P cell migration to the ventral cord during the first larval stage. Expression of
rho-1 (dn) causes a strong P cell migration defect. This effect appears to be specifically the result of
rho-1 inhibition since expression of the C3 exoenzyme causes a similar P cell phenotype. Genetic and biochemical analyses of
unc-73, a GDP/GTP exchange factor, indicate that
unc-73 acts as an exchange factor for
rho-1 during P cell migration in vivo. Another rho family GTPase,
mig-2, is not required for P cell migrations but may contribute to a common pathway with
rho-1 in some manner. This is based on observations that (a)
mig-2 null alleles exacerbate a weak P cell migration defect in
unc-73 mutants (Zipkin, et al., 1997), which is partially rescued by
rho-1 (gf) (Zipkin, Kindt, and Keynon, 19971), and (b)
mig-2 gain-of-function alleles cause a P cell migration defect, presumably by interfering with members of the
rho-1 pathway. In order to identify molecules acting downstream of
rho-1 during P cell migration, we have studied multiple alleles of
let-502. Putative null alleles of
let-502 and
let-502 RNAi result in a weak P cell migration defect in worms surviving to L2. A temperature-sensitive hypomorphic allele causes a similar P cell phenotype. We propose that
unc-73 and
rho-1 act together, partially through
let-502, to direct P cell migration in C. elegans. 1 Zipkin, Ilan D., Rachel M. Kindt, and Cynthia J. Kenyon Cell 1997 90: 883-894.