MIG-21 interacts with Wnt and Netrin signaling in gonad migration in C. elegans.

The gonad of Caenorhabditis elegans hermaphrodites is a longstanding model of cell migration, stem cell niche function, and organogenesis, but it has not yet been investigated using single-cell RNA-sequencing (scRNA-seq). Using a recently published scRNA-seq dataset of adult C. elegans hermaphrodites, we identified a previously unknown regulator of the leader cell of gonad migration (the distal tip cell, or DTC). The gene mig-21 is both highly and specifically expressed in the DTC, yet has no known role in that cell. However, mig-21 regulates cell migration in other developmental contexts. Using classical genetics techniques, RNAi knockdown, and live cell imaging, we discovered that mig-21 acts synergistically with the Wnt and Netrin pathways to guide anteroposterior and dorsoventral phases of migration in the DTC at the level of signaling, not DTC cell structure. Known interactors of mig-21 in other cell types-like PTP-3C-also act with MIG-21 in DTC migration. Despite its expression in stationary adult DTCs, mig-21 does not play a role in the cessation of DTC migration but instead seems to impart continued sensitivity of the DTC to Wnt and Netrin in adulthood. This study reveals additional complexity of signaling integration between major regulators of germline stem cell niche migration, and as a proof of concept it demonstrates the utility of scRNA-seq datasets in revealing testable hypotheses about genetic networks that were masked by redundancy in traditional screening methods.