Organs are often formed by elongation and branching of epithelial tubes. Although regulation of initiation and direction of epithelial tube migration is an important aspect in organogenesis, there must be mechanisms that terminate epithelial migration to generate organs of appropriate size. These mechanisms remain mostly unexplored, however. The gonadal development in C. elegans offers a simple model system to study the morphogenesis by epithelial tubes. The migration of the anterior and posterior gonadal leader cells called distal tip cells (DTCs) promote directional elongation of gonad arms during larval development and form a pair of U-shaped gonad arms in rotational symmetry. We placed Venus under the control of the DTC specific
mig-24 promoter and fluorescently visualized DTCs. In the wild type adult worms, two DTCs stopped around the dorsal side of the vulva. We isolated two mutants,
tk102 and
tk107 by EMS mutageneis. About 80% of DTCs in these mutants overshot the vulval region, but fewer than 10% of DTCs did in the wild type. Both of these mutants are recessive and they partially complement each other. These mutants seem not to affect growth rate, animal size and behavior. To understand the difference in migration modes of DTCs between the wild type and the mutants, we analyzed the timing of DTC turns and migration speed of DTCs. We found that DTCs in these mutants make two turns at the same timing as in the wild type, but that the deceleration rates of mutant DTCs after the second turn were decreased compared to the wild type. Thus the DTCs in the mutants fail to stop at the normal timing. Interestingly, we found that the expression of
mig-24::Venus, which is normally weakened after stopping of DTCs at the young adult stage, was retained to be strong even in the 2-day-old adults in
tk107.
mig-24 encodes a transcription factor of the bHLH family. Genetic mapping experiments assigned
tk102 and
tk107 to 2473kb and 1853kb overlapping regions of the chromosome III, respectively. Deep sequencing analysis revealed a nonsense mutation in the predicted gene F42H10.5 in the
tk107 genome. RNAi knockdown of this gene resulted in an overshoot phenotype similar to that observed in
tk107. We also successfully rescued
tk107 by a fosmid clone. F42H10.5 appears to encode a Zink-finger DNA-binding protein having weak homology to ZBED4 in mammals. Therefore, it is possible that F42H10.5 is a negative transcriptional regulator of
mig-24 which could act in promotion of DTC migration.