Cells and axons respond to extrinsic guidance cues by directed movement, but how guidance information actually regulates the cytoskeletal components that control movement is not known. The anterior migrations of the QR descendants are controlled cell-extrinsically by a novel transmembrane protein, MIG-13; in
mig-13 mutants, these migrations are shortened (work of Mary Sym). We found that the QR cell descendants migrate more slowly in
mig-13 mutants. This result suggests that the cell's "motility machinery" is indeed altered by the presence or absence of guidance information. The Rho GTPase
mig-2 is a good candidate for a component of the motility machinery: in null or putative activated
mig-2 mutants the migrations of the QR descendants are shortened, but the direction of migration is never altered. Since QR descendants in
mig-2 mutants migrate farther than in
mig-13 mutants, we were surprised to find that in
mig-13 mig-2(activated or null) double mutants the cells moved a shorter distance than in
mig-13 alone. This finding suggests that migrating cells determine their final positions by somehow integrating the available guidance information (which influences both direction and speed of their migration), and then using the motility machinery to execute the decision. Integrin receptors containing the
pat-3 beta integrin subunit are likely to act with
mig-2 , based on the phenotypes of a new, viable
pat-3 allele, and of transgenic worms in which the embryonic lethality of
pat-3(null) mutants is rescued by muscle-specific expression of PAT-3. Axonal growth cones may use mechanisms similar to those of migrating cells to select and execute their direction of movement. However, the role of
mig-2 and
pat-3 appears to be different in growth cones: in both activated
mig-2 mutants and animals carrying our new
pat-3 allele, the HSN axon grows but is not correctly guided. In contrast, in the cell migrations described above, these mutations alter movement but not guidance. This finding suggests that the wild-type function of these genes in the HSN axon may be to transmit guidance signals (perhaps mediated by
unc-40 and
sax-3 ) rather than to permit movement per se.