Repulsive Guidance Molecule Acts in Axon Branching inCaenorhabditis elegans

ABSTRACT Repulsive guidance molecules (RGMs) are evolutionarily conserved proteins implicated in repulsive axon guidance. Here we report the function of the Caenorhabditis elegans ortholog DRAG-1 in axon branching. The axons of hermaphrodite-specific neurons (HSNs) branch at the region abutting the vulval muscles and innervate these muscles to control egg laying. The drag - 1 mutants exhibited defects in HSN axon branching in addition to a small body size and egg laying–defective phenotype. DRAG-1 expression in the hypodermal cells was required for the branching of these axons. The C-terminal glycosylphosphatidylinositol anchor of DRAG-1 was important for its function. Genetic analyses suggested that the membrane receptor UNC-40, but neither SMA-1/β H -spectrin nor SMA-5/MAP kinase 7, acts in the same pathway with DRAG-1 in HSN branching. We propose that DRAG-1 expressed in the hypodermis signals via the UNC-40 receptor expressed in HSNs to elicit branching activity of HSN axons.