TY - JOUR TI - Completion of neural crest cell production and emigration is regulated by retinoic-acid-dependent inhibition of BMP signaling AU - Rekler, Dina AU - Kalcheim, Chaya A2 - LaBonne, Carole A2 - Stainier, Didier YR A2 - Kerosuo, Laura VL - 11 PY - 2022 DA - 2022/04/08 SP - e72723 C1 - eLife 2022;11:e72723 DO - 10.7554/eLife.72723 UR - https://doi.org/10.7554/eLife.72723 AB - Production and emigration of neural crest cells is a transient process followed by the emergence of the definitive roof plate. The mechanisms regulating the end of neural crest ontogeny are poorly understood. Whereas early crest development is stimulated by mesoderm-derived retinoic acid, we report that the end of the neural crest period is regulated by retinoic acid synthesized in the dorsal neural tube. Inhibition of retinoic acid signaling in the neural tube prevents the normal upregulation of BMP inhibitors in the nascent roof plate and prolongs the period of BMP responsiveness which otherwise ceases close to roof plate establishment. Consequently, neural crest production and emigration are extended well into the roof plate stage. In turn, extending the activity of neural crest-specific genes inhibits the onset of retinoic acid synthesis in roof plate suggesting a mutual repressive interaction between neural crest and roof plate traits. Although several roof plate-specific genes are normally expressed in the absence of retinoic acid signaling, roof plate and crest markers are co-expressed in single cells and this domain also contains dorsal interneurons. Hence, the cellular and molecular architecture of the roof plate is compromised. Collectively, our results demonstrate that neural tube-derived retinoic acid, via inhibition of BMP signaling, is an essential factor responsible for the end of neural crest generation and the proper segregation of dorsal neural lineages. KW - quail KW - neural crest KW - roof plate KW - retinoic acid KW - bmp KW - somite JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -