Regulation of neural progenitor cell state by ephrin-B.
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.
Division of Neurosciences, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
Runxiang
R
Qiu
Xiuyun
X
Wang
Alice
A
Davy
Chen
C
Wu
Kiyohito
K
Murai
Heying
H
Zhang
John G
JG
Flanagan
Philippe
P
Soriano
Qiang
Q
Lu
D000818:Animals; D002454:Cell Differentiation; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology; D036342:Ephrins / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D020710:RGS Proteins; D036081:Receptors, Eph Family / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
D036342:Ephrins; D020690:GTPase-Activating Proteins; D020710:RGS Proteins; C415085:Rgs3 protein, mouse; D036081:Receptors, Eph Family; D019204:GTP-Binding Proteins