Multiple ephrins control cell organization in C-elegans using kinase-dependent and -independent functions of the VAB-1 Eph receptor

Eph receptor (EphR) tyrosine kinases and their ephrin ligands mediate direc t cell-to-cell signaling. The C. elegans genome encodes four potential GPI- modified ephrins (EFN-1 to -4) and one EphR (VAB-1). Single and multiple ep hrin mutants reveal functions for EFN-1, EFN-2, and EFN-3 in epidermal cell organization that, in aggregate, mirror those of VAB-1. Ephrin mutants hav e defects in head morphology and enclosure of the embryo by the epidermis a nd identify ephrin-EphR signaling functions involved in aligning and fusing tail and head epidermal cells, respectively. Biochemical analyses indicate that EFN-1, EFN-2, and EFN-3 jointly activate the VAB-1 tyrosine kinase in vivo. Mutant phenotypes and expression pattern analysis suggest that multi ple ephrins are involved in distinct aspects of kinase-dependent and kinase -independent VAB-1 signaling required for proper cell organization during d evelopment in C. elegans.