Regulation of neural progenitor cell state by ephrin-B.

Publication Type:

Journal Article

Source:

The Journal of cell biology, Volume 181, Issue 6, p.973-83 (2008)

Keywords:

2008, Animals, Basic Sciences Division, Cell Differentiation, Cerebral Cortex, EPHRINS, GTP-Binding Proteins, GTPASE-ACTIVATING PROTEINS, MICE, NEURONS, Receptors, Eph Family, Signal Transduction, Stem Cells

Abstract:

Maintaining 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.