C. elegans cell migration gene mig-10 shares similarities with a family of SH2 domain proteins and acts cell nonautonomously in excretory canal development.

The mig-10 gene of Caenorhabditis elegans is required for the long-range anteroposterior migration of embryonic neurons CAN, ALM, and HSN and proper development of the excretory canals. Here, we report the cloning and initial molecular characterization of mig-10. The predicted MIG-10 proteins share a large region of similarity with a recently identified family of mammalian SH2 domain proteins, Grb7 and Grb10. We call this region of similarity the GM region (for Grb and Mig). MIG-10 proteins do not contain an SH2 domain, but share with the Grbs a pleckstrin homology (PH) domain and proline-rich regions, features commonly found in signal transduction proteins. The functions of Grb7 and Grb10 are unknown, but Grb7 is overexpressed in certain breast cancers, where it is bound to the growth factor receptor HER2, while Grb10 has been implicated in insulin signaling. We also report the isolation of a new mig-10(e2527) allele, as well as the molecular characterization of e2527 (splice acceptor mutation) and the canonical ct41 (amber) allele. Finally, we report the results of a genetic mosaic analysis which reveal that mig-10 acts cell nonautonomously in the development of the excretory canals and suggest a possible focus for mig-10 activity within descendants of the AB cell lineage. Elucidation of the role of mig-10 in C. elegans development should lead to a better understanding of cell migration and may shed light on the function of a family of SH2 domain proteins apparently involved in signal transduction and cancer.