Cell adhesion molecules of the Immunoglobulin Superfamily (IgCAMs) are key factors in nervous system formation. The contactin subgroup of IgCAMs consists of GPI-anchored glycoproteins implicated in axon outgrowth, guidance, fasciculation and neuronal differentiation. The mechanism by which contactins facilitate neuronal development is not understood. To gain insight into the function of contactins, we characterized RIG-6, the sole contactin of Caenorhabditis elegans. We show that the contactin RIG-6 is involved in excretory cell (EC) tubular elongation. We also show that RIG-6 mediates axon outgrowth and guidance along both the anterior-posterior and dorso-ventral axis, during C. elegans development. We find that optimal RIG-6 expression is critical for accurate mechanosensory neuron axon elongation and ventral nerve cord architecture. In addition, our data suggest that the cytoplasmic UNC-53/NAV2 proteins may contribute to relay signaling via contactins.
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