The Transmembrane Receptor UNC-40 Directs Muscle Arm Extension in Caenorhabditis elegans

In Caenorhabditis elegans, body muscles extend muscle arms in a chemotropic fashion to the nearest nerve cord and serves as a model for the investigation of guided cell migration. I found that the transmembrane receptor UNC-40/DCC is required, and functions cell-autonomously to regulate muscle arm extension. Surprisingly, both the canonical ligand of UNC-40 (UNC-6/Netrin) and the extracellular domains of UNC-40 are dispensable, suggesting that UNC-40 relies on a co-receptor or other polarizing pathways to direct muscle arm extension. Furthermore, through double mutant analyses and the use of a neomorphic phenotype induced by UNC-40 over-expression, I define a distinct UNC-40 pathway in which UNC-73/Trio, the WAVE actin polymerization complex, and components of the dense body likely act downstream of UNC-40 to regulate muscle arm extension. Distinct modes of UNC-40’s function in muscle arm extension compared to its role in neurons provide a more complete understanding of how this conserved guidance receptor functions.MAS