Distal Tip Cells (DTCs) are located at the tip of gonadal arms in hermaphrodites and guide gonadal arm extensions during larval development. During migration, DTCs first move to the end of the body along the ventral side (phase I), then make a dorsal turn (phase II) and finally migrate back to the mid-body along the dorsal side (phase III). We isolated
dpy-24 mutants via their DTC-migration defect. The DTCs of
dpy-24 mutants undergo a precocious dorsal turn. Previous studies showed that UNC-5, a receptor of UNC-6/netrin ligand, was required and sufficient for the dorsal migration of DTCs (1 and 2). Our genetic studies indicate that the Dpy-24 DTC defect requires
unc-5 activity. Using the Punc-5::gfp transgene, we found that
unc-5 was expressed earlier in DTCs of
dpy-24 mutants than those of wild type and that the timing of
unc-5 expression in
dpy-24 mutants correlates well with the precocious dorsal turn of DTCs. Therefore, the Dpy-24 DTC defect was likely caused by the premature expression of
unc-5. DPY-24 contains a PR domain and five zinc fingers and is similar to human PRDI-BF1 and mouse Blimp-1. These mammalian proteins have been shown to function as transcription repressors during B lymphocyte maturation. We raised antibodies against DPY-24. DPY-24 was detected in DTCs prior to their dorsal turn. After DTCs migrated dorsally, no DPY-24 was detected in these cells. Interestingly, the constitutive expression of
dpy-24 in DTCs partially blocked DTC dorsal turn. These results together indicate that the DPY-24 level controls DTC dorsal turn. The
daf-12 gene encodes a nuclear hormone receptor and is required for
unc-5 expression (3). The genetic analysis of
dpy-24;
daf-12 double mutants showed that
dpy-24 and
daf-12 partially suppressed each others phenotypes in DTC dorsal turn, suggesting that
dpy-24 and
daf-12 may act together to control DTC dorsal migration. Our data are consistent with the model that during phase I of DTC migration, DPY-24 prevents DAF-12 from transcriptionally activating
unc-5. Whereas in phase II, the DPY-24 level drops, hence allowing DAF-12 to activate
unc-5 expression, which, in turn, drives DTC migrates dorsally. References: (1)Leung-Hagesteijn et al. (1992) Cell 71, 289-99 (2)Su et al. (2000) Development 127, 585-94. (3)Antebi et al. (2000) Genes & Development 14, 1512-1527.