Novel genes controlling ventral cord asymmetry and navigation of pioneer axons in C. elegans

The ventral cord in C. elegans is the major longitudinal axon tract containing essential components of the motor circuit. In genetic screens using transgenic animals expressing neuron specific GFP reporters, we identified twelve genes required for the correct outgrowth of interneuron axons of the motor circuit. In mutant animals, axons fail to navigate correctly towards the ventral cord or fail to fasciculate correctly within the ventral cord. Several of those mutants define previously uncharacterized genes. Two of the genes, ast-4 and ast-7, are involved in the generation of left-right asymmetry of the two ventral cord axon tracts. Three other genes specifically affect pioneer-follower relationships between early and late outgrowing axons, controlling either differentiation of a pioneer neuron (lin-11) or the ability of axons to follow a pioneer (ast-2, unc-130). Navigation of the ventral cord pioneer neuron AVG itself is defective in ast-4, ast-6 and unc-130 mutants. Correlation of these defects with navigation defects in different classes of follower axons revealed a true pioneer role for AVG in the guidance of interneurons in the ventral cord. Taken together, these genes provide a basis to address different aspects of axon navigation within the ventral cord of C. elegans.