Qiu, RunxiangWang, XiuyunDavy, AliceWu, ChenMurai, KiyohitoZhang, HeyingFlanagan, JohnSoriano, PhilippeLu, Qiang2012-02-142008Qiu, Runxiang, Xiuyun Wang, Alice Davy, Chen Wu, Kiyohito Murai, Heying Zhang, John G. Flanagan, Philippe Soriano, and Qiang Lu. 2008. Regulation of neural progenitor cell state by ephrin-B. The Journal of Cell Biology 181(6): 973-983.0021-9525http://nrs.harvard.edu/urn-3:HUL.InstRepos:8160871Maintaining a balance between self-renewal and differentiation in neural progenitor cells during development is important to ensure that correct numbers of neural cells are generated. We report that the ephrin-B–PDZ-RGS3 signaling pathway functions to regulate this balance in the developing mammalian cerebral cortex. During cortical neurogenesis, expression of ephrin-B1 and PDZ-RGS3 is specifically seen in progenitor cells and is turned off at the onset of neuronal differentiation. Persistent expression of ephrin-B1 and PDZ-RGS3 prevents differentiation of neural progenitor cells. Blocking RGS-mediated ephrin-B1 signaling in progenitor cells through RNA interference or expression of dominant-negative mutants results in differentiation. Genetic knockout of ephrin-B1 causes early cell cycle exit and leads to a concomitant loss of neural progenitor cells. Our results indicate that ephrin-B function is critical for the maintenance of the neural progenitor cell state and that this role of ephrin-B is mediated by PDZ-RGS3, likely via interacting with the noncanonical G protein signaling pathway, which is essential in neural progenitor asymmetrical cell division.en-USJournal Article2012-02-1410.1083/jcb.200708091