Muscle cell migrations of C. elegans are mediated by the alpha-integrin INA-1, Eph receptor VAB-1, and a novel peptidase homologue MNP-1

Cell migration is a fundamental process occurring during embryonic development and tissue morphogenesis. In the nematode Caenorhabditis elegans, morphogenesis of the body-wall musculature involves short-range migrations of 81 embryonic muscle cells from the lateral surface of the embryo towards the dorsal and ventral midlines. This study shows that mutations in ina-1 (α-integrin), as well as vab-1 (Eph receptor), and vab-2 (ephrin), display defects in embryonic muscle cell migration. Furthermore, an RNAi-based enhancer screen in an ina-1 weak loss-of-function background identified mnp-1 (matrix non-peptidase homologue-1) as a previously uncharacterized gene required for promoting proper migration of the embryonic muscle cells. mnp-1 encodes a membrane associated metalloproteinase homologue that is predicted to be catalytically inactive. Our data suggest that MNP-1 is expressed in migrating muscle cells and localizes to the plasma membrane with the non-peptidase domain exposed to the extra-cellular environment. Double-mutant analysis between mnp-1(RNAi), ina-1, and vab-1 mutations; as well as tissue specific rescue experiments; indicated that each of these gene products function predominantly independent of each other and from different cell types to affect muscle cell migration. Together these results suggest complex interactions between the adjacent epidermal, neuronal, and muscle cells are required to promote proper muscle cell migration during embryogenesis.