The unc-53 gene negatively regulates rac GTPases to inhibit unc-5 activity during Distal tip cell migrations in C. elegans.

The unc-53/NAV2 gene encodes for an adaptor protein required for cell migrations along the anteroposterior (AP) axes of C. elegans. This study identifies unc-53 as a novel component of signaling pathways regulating Distal tip cell (DTC) migrations along the AP and dorsoventral (DV) axes. unc-53 negatively regulates and functions downstream of ced-10/Rac pathway genes; ced-10/Rac and mig-2/RhoG, which are required for proper DTC migration. Moreover, unc-53 exhibits genetic interaction with abl-1 and unc-5, the 2 known negative regulators of ced-10/Rac signaling. Our genetic analysis supports the model, where abl-1 negatively regulates unc-53 during DTC migrations and requirement of unc-53 function during both AP and DV DTC migrations could be due to unc-53 mediated regulation of unc-5 activity.