Roles for netrin signaling outside of axon guidance: a view from the worm

The Netrin family of extracellular ligands and their receptors were the first identified signaling pathway regulating axon guidance. Subsequent work across model systems has begun to reveal the interactions that take place downstream of Netrin reception to facilitate growth cone migration. Though intensely studied, many aspects of this signaling system remain unclear. Even less understood are the growing number of contexts in which Netrin signaling influences cells beyond axon guidance and even outside the nervous system. Genetic and cell-biological studies in C. elegans have played an instrumental role in identifying critical functions for Netrin ligands in setting up specialized and potentially adhesive membrane-associated domains within a broad range of cell types. Here we review recent literature implicating Netrin or its receptors in morphogenetic processes outside of growth cone regulation with a special focus on studies in C. elegans that suggest cell biological mechanisms for Netrin signaling.