Axons are guided to their targets in the developing nervous system by the growth cone. In response to guidance receptor signals, the growth cone actin cytoskeleton is modulated to achieve growth cone movement. The actin cytoskeleton can mediate diverse functions in the growth cone, including guidance and the rate of outgrowth. The Arp2/3 complex is a major actin-nucelating complex and is involved in many morphogenetic processes including Drosophila axon pathfinding (Zallen et al., 2002, Pollard et al., 2000). Scar/WAVE is an activator of Arp2/3 complex that has extensive homology with WASP-Homology (WH) proteins in its C-terminal domain and a Scar-specific N-terminal Scar homology domain (SHD). Rac small GTPases are known to activate Arp2/3 actin nucleation via Scar, but the interactions of these molecules during axon development remain unclear. We have undertaken a study of the role of the C. elegans Scar gene
wve-1 in axon pathfinding. A fusion of the
wve-1 promoter and the SHD coding region to gfp was expressed in most cells in early embryogenesis. At the two-fold stage of elongation,
wve-1::gfp expression was prominent in the nerve ring, suggesting that
wve-1 is expressed in neurons. To determine if
wve-1 is required for axon development, we ablated
wve-1 gene function by RNAi.
wve-1(RNAi) caused approximately 60% early embryonic lethality. The arrested embryos displayed morphogenesis defects as early as gastrulation, suggesting
wve-1 is important for proper embryonic morphogenesis. However, viable
wve-1(RNAi) progeny displayed no axon development defects. Three C. elegans rac genes
ced-10,
mig-2 and
rac-2/3 act redundantly in axon development. To determine if
wve-1 acts redundantly with
mig-2 and
ced-10 in axon development, we performed
wve-1 RNAi in
mig-2 and
ced-10 mutants. In both cases, embryonic arrest increased to ~80%, indicating that
wve-1 and the racs might act together during embryonic morphogenesis. Furthermore,
wve-1(RNAi);
mig-2 viable animals displayed axon development defects, most notably ectopic axon branching, whereas
wve-1(RNAi);
ced-10 viable animals did not, suggesting that
wve-1 acts in parallel to
mig-2 rac but not
ced-10 rac during axon development. Analysis of
wve-1;
ced-10 and
wve-1;
mig-2 double mutants showed similar results. Thus,
wve-1 might be required for embryonic morphogenesis and might function redundantly with
mig-2 rac in axon development, possibly in the
ced-10 rac pathway.