Mutations in
unc-34 partially disrupt the migrations of cells and axon growth cones and the fasciculation of axons into nerve bundles. We have found that
unc-34 encodes a homolog of the Drosophila Enabled (Ena) and mouse Mena proteins that have been implicated in regulating cytoskeletal dynamics though F-actin assembly (Dell et al. 1998 WCWM Abstract). In Drosophila , ena is necessary for axon outgrowth and fasciculation. Our results show that in C. elegans Ena also functions in cell migration. The weak effects of
unc-34 null mutations on cell and growth cone migrations suggest that additional genes act to regulate actin assembly. In RNAi experiments, we have found that a gene similar to Drosophila disabled ( dab ) and a gene encoding a homolog of the Wiskcott-Aldridge Syndrome Protein (WASP) act in parallel to
unc-34 to regulate cell motility. In Drosophila , Disabled (Dab) is a negative regulator of Ena. In C. elegans , in contrast, we have found that a dab -like gene appears to act in parallel to
unc-34 . RNAi experiments with dab result in cell migration defects, and dab(RNAi) in an
unc-34 null mutant results in cell migration defects that are more severe than in either an
unc-34 or dab(RNAi) background. WASP has also been implicated in cytoskeletal dynamics. In addition, Ena and WASP have an EVH1 domain at their amino termini which binds vinculin and zyxin. wasp(RNAi) animals display no obvious phenotypes, but wasp(RNAi) in
unc-34 null mutants results in synthetic lethality. Most animals die as embryos, and the few embryos that hatched were too disorganized to score the positions of migratory cells. To test whether wasp was involved in cell motility, we injected wasp RNA into
unc-34(
e315 ts ) . At the permissive temperature many of the embryos hatched and these animals were found to have severe cell migration defects. We are currently screening for mutations that are synthetically lethal with
unc-34 .