Characterization of dpy-24(tk41) and mechanism of DPY-24 down-regulation in distal tip cell migration in Caenorhabditis elegans

Abstract

Cell migration is critical for organogenesis during animal development. Patterned migration of gonadal distal tip cells (DTCs) in Caenorhabditis elegans is an ideal model for cell migration research. DTCs have three sequential migration phases. During phase I, DTCs migrate along the ventral body wall muscle in the L1 and L2 stages. At mid-L3, DTCs reorient and migrate dorsalward during phase II. In phase III, DTCs turn orthogonally and migrate along the dorsal body wall muscle toward midbody in the late L3 and L4 stages. Several factors have been identified and characterized that regulate DTC migration in temporally and spatially specific fashions. For example, UNC-5/Netrin receptor has been shown to act in DTCs to guide their phase II dorsal migration against the ventrally concentrated repellent of UNC-6/Netrin. Three heterochronic-related proteins, transcription factors LIN-29 and DAF-12 and F-box protein DRE-1, act redundantly to control the reflexion of the gonad in L3. Our lab has identified a zinc-finger-containing protein DPY-24 that functions to suppress the initiation of phase II migration in phase I by transcriptionally repressing unc-5. In this study, we have genetically and molecularly defined a new allele of dpy-24, tk41. In addition, we found that dpy-24 acts synergistically with unc-5 and unc-6 to regulate the phase III migration direction. This observation shows a previously unassigned function of unc-5 and unc-6 in the longitudinal DTC migration. Furthermore, DPY-24 protein is detected in phase I but not phase II or III in wild type; however, daf-12 and dre-1 double mutations block the down-regulation of DPY-24 in phase II and III. This result reveals a complex regulation of the DPY-24 level in specifying the timing of phase II migration.