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. 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
scr-1 in axon pathfinding.A fusion of the
scr-1 promoter and the SHD coding region to gfp was expressed in most cells in early embryogenesis. At the two-fold stage of elongation,
scr-1::gfp expression was prominent in the nerve ring, suggesting that
scr-1 is expressed in neurons. To determine if
scr-1 is required for axon development, we ablated
scr-1 gene function by RNAi.
scr-1(RNAi) caused approximately 60% early embryonic lethality. The arrested embryos displayed morphogenesis defects as early as gastrulation, suggesting
scr-1 is important for proper embryonic morphogenesis. However, viable
scr-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
scr-1 acts redundantly with
mig-2 and
ced-10 in axon development, we performed
scr-1 RNAi in
mig-2 and
ced-10 mutants. In both cases, embryonic arrest increased to ~80%, indicating that
scr-1 and the racs might act together during embryonic morphogenesis. Furthermore,
scr-1(RNAi);
mig-2 viable animals displayed axon development defects, most notably ectopic axon branching, whereas
scr-1(RNAi);
ced-10 viable animals did not, suggesting that
scr-1 acts in parallel to
mig-2 rac but not
ced-10 rac during axon development. Thus,
scr-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.