P-09 Rho signaling pathway regulates the migration of cultured rat neural crest cells

摘要

The inhibition of neural crest cell (NCC) migration has been considered as a possible pathogenic mechanism underlying chemical developmental toxicity. So far, we found several developmentally toxic chemicals inhibited the migration of rat NCCs at their embryotoxic concentrations using a simple in vitro assay that we established. In the present study, we investigated the migratory mechanisms of NCCs that developmentally toxic chemicals can affect, using the inhibitor and activator of the Rho signaling pathway. Rat NCCs were cultured as emigrated cells from neural tubes of rat embryos at day 10.5 of gestation. At 24 h of culture, the inhibitors or activators were added to the culture medium. The migration distance of the neural crest cells was determined as the ratio of radii calculated from areas outlined by connecting most outside neural crest cells at 24 and 48 h of culture, respectively. The NCC migration was promoted by the inhibitor of the Rho signaling pathway, but was inhibited by the activator. In addition, the NCC migration was greatly promoted by the inhibitor of ROCK, a downstream effector of Rho. It was considered from these results that the Rho signaling pathway regulated the NCC migration through Rho-ROCK signaling.