| Popis: |
The enteric nervous system (ENS) is a vast intrinsic network of neurons and glia within the gastrointestinal tract and is largely derived from enteric neural crest cells (ENCCs) that emigrate into the gut during vertebrate embryonic development. Study of ENCC migration dynamics and their genetic regulators provides great insights into fundamentals of collective cell migration and nervous system formation, and are a pertinent subject for study due to their relevance to the human congenital disease, Hirschsprung disease (HSCR). For the first time, we performedin totogut imaging and single-cell generation tracing of ENCC migration in WT and a novelretheterozygous background zebrafish (retwmr1/+) to gain insight into ENCC dynamicsin vivo. We observed thatretwmr1/+zebrafish produced fewer ENCCs while localized along the gut, which failed to reach the hindgut, resulting in HSCR-like phenotypes. Specifically, we observed a proliferation dependent migration mechanism, where cell divisions were associated with inter-cell distances and migration speed. Lastly, we detected a premature neuronal differentiation gene expression signature inretwmr1/+ENCCs, collectively suggesting that Ret signaling may function to regulate maintenance of a stem-state in ENCCs. |
