mls-2 and vab-3 control glia development, hlh-17/Olig expression and glia-dependent neurite extension in C-elegans

Glia are essential components of nervous systems. However, genetic programs promoting glia development and regulating glia-neuron interactions have not been extensively explored. Here we describe transcriptional programs required for development and function of the C. elegans cephalic sheath (CEPsh) glia. We demonstrate ventral-and dorsal-restricted roles for the mls-2/Nkx/Hmx and vab-3/Pax6/Pax7 genes, respectively, in CEPsh glia differentiation and expression of the genes hlh-17/Olig and ptr-10/Patched-related. Using mls-2 and vab-3 mutants, as well as CEPsh glia-ablated animals, we show that CEPsh glia are important for sensory dendrite extension, axon guidance/branching within the nerve ring, and nerve ring assembly. We demonstrate that UNC-6/Netrin, expressed in ventral CEPsh glia, mediates glia-dependent axon guidance. Our results suggest possible similarities between CEPsh glia development and oligodendrocyte development in vertebrates, and demonstrate that C. elegans provides a unique environment for studying glial functions in vivo.