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-ran ge anteroposterior migration of embryonic neurons CAN, ALM, and HSN an d proper development of the excretory canals. Here, we report the clon ing and initial molecular characterization of mig-10. The predicted MI G-10 proteins share a large region of similarity with a recently ident ified family of mammalian SH2 domain proteins, Grb7 and Grb10. We call this region of similarity the GM region (for Grb and Mig). MIG-10 pro teins do not contain an SH2 domain, but share with the Grbs a pleckstr in homology (PII) domain and proline-rich regions, features commonly f ound in signal transduction proteins. The functions of Grb7 and Grb10 are unknown, but Grb7 is overexpressed in certain breast cancers, wher e it is bound to the growth factor receptor HER2, while Grb10 has been implicated in insulin signaling. We also report the isolation of a ne w mig-10(e2527) allele, as well as the molecular characterization of e 2527 (splice acceptor mutation) and the canonical ct41 (amber) allele. finally, we report the results of a genetic mosaic analysis which rev eal that mig-10 acts cell nonautonomously in the development of the ex cretory 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 ce ll migration and may shed light on the function of a family of SH2 dom ain proteins apparently involved in signal transduction and cancer. (C ) 1997 Academic Press.