Gα subunit coordinates with ephrin-B to balance self-renewal and differentiation in neural progenitor cells.
Proper development of the mammalian brain requires that neural progenitor cells balance self-renewal and differentiation under precise temporal and spatial regulation, but the underlying mechanisms are not well understood. In this study, we identify Gα subunit as a positive regulator of mammalian neurogenesis, working with the regulator of G protein signaling (RGS)-mediated ephrin-B signaling pathway as two opposing forces to maintain a balance between self-renewal and differentiation in the developing mouse cerebral cortex. Multiple Gα(i) subunits are expressed by cortical neural progenitor cells during the course of cortical neurogenesis. Activation of Gα(i) signaling, through in utero electroporation-mediated expression of wild-type and constitutively active Gα(i) subunits, counteracts the function of ephrin-B in cortical neural progenitors to induce differentiation. Genetic knock-in of an RGS-insensitive G184SGα(i2) causes early cell cycle exit and a reduction of cortical neural progenitor cells and leads to a defect in the production of late born cortical neurons, similar to what is observed in mutant mice with deficiency in ephrin-B reverse signaling pathway. This study reveals a role of Gα subunit in mammalian neurogenesis and uncovers a developmental mechanism, coordinated by the Gα and ephrin-B signaling pathways, for control of the balance between self-renewal and differentiation in neural progenitor cells.
Murai
Kiyohito
K
Department of Neurosciences, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA.
Qiu
Runxiang
R
Zhang
Heying
H
Wang
Jun
J
Wu
Chen
C
Neubig
Richard R
RR
Lu
Qiang
Q
D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000196:embryology / Q000378:metabolism*; D018274:Electroporation; D053595:Embryonic Stem Cells / Q000378:metabolism*; D036342:Ephrins / Q000378:metabolism*; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism*; D020710:RGS Proteins / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors
D036342:Ephrins; D020710:RGS Proteins; D051960:GTP-Binding Protein alpha Subunit, Gi2