20-P008 Regulation of neuronal migration by proneural GTP-binding protein pathways

During development, the pancreatic endocrine cells are specified within the epithelium. They will subsequently delaminate and migrate out of the epithelium in order to form the islets. Neurogenin3 (Ngn3) is a bHLH transcription factor that is responsible for differentiation of all endocrine cell types, but whether or not it has a role in their migration is still an open question. By using the chicken embryo model organism, we found that differentiation and migration programs are two different processes that are induced by Ngn3 and that can be uncoupled. Therefore, we tried to unravel the mechanisms by which Ngn3 can induce endocrine cell migration. We found that, both in chick and mouse models, overexpression of Ngn3 induces a loss of apico-basal polarity, a breakdown of basal lamina, and more importantly, a loss of the epithelial marker E-cadherin (Ecad). We also found that this is not a direct effect mediated by E-boxes in the Ecad promoter. Therefore, we are currently trying to find targets of Ngn3 that could mediate repression of Ecad, focalizing on the zinc-finger transcription factors Snail and Slug. Moreover, we are also using a pancreatic explant culture method, developed in the laboratory of Pr. Jonathan Slack, that allows us to do time-lapse imaging. Taking advantage of our Pdx::Ngn3 transgenic line, we are following Ngn3 overexpressing cells to understand in a more physiological manner how they migrate in the developing pancreas.