VAB-8 IS A KEY REGULATOR OF POSTERIORLY DIRECTED MIGRATIONS IN C-ELEGANS AND ENCODES A NOVEL PROTEIN WITH KINESIN MOTOR SIMILARITY

Nervous system assembly requires the directed migrations of cells and axon growth cones along the dorsoventral and anteroposterior axes. Alt hough guidance mechanisms for dorsoventral migrations are conserved fr om nematodes to mammals, mechanisms for anteroposterior migrations are unknown. In C. elegans, the gene vab-8, which specifically functions in posteriorly directed migrations, encodes two isoforms of a novel in tracellular protein that act cell-autonomously in different migrations . VAB-8L, which contains a domain similar to kinesin-like motors, func tions in all vab-8-dependent axon growth cone migrations. VAB-8S, whic h lacks this N-terminal domain, functions in a subset of vab-8-depende nt cell migrations. Continuous expression of VAB-8L in the ALM mechano sensory neuron, which normally requires vab-8 early in its development for posteriorly directed cell migration, redirects its anteriorly pro jecting axon posteriorly. We propose that regulation of vab-8 activity is a mechanism for controlling the direction of cell and axon growth cone migrations.