期刊
STEM CELLS
卷 28, 期 9, 页码 1581-1589出版社
WILEY
DOI: 10.1002/stem.474
关键词
G alpha; subunit; Ephrin-B/RGS signaling; Neural progenitor cells; Cortical neurogenesis; Self-renewal and differentiation
资金
- NIH [NS52388, GM39561]
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 G alpha 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 G alpha(i) subunits are expressed by cortical neural progenitor cells during the course of cortical neurogenesis. Activation of G alpha(i) signaling, through in utero electroporation-mediated expression of wild-type and constitutively active G alpha(i) subunits, counteracts the function of ephrin-B in cortical neural progenitors to induce differentiation. Genetic knock-in of an RGS-insensitive G184SG alpha(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 Ga subunit in mammalian neurogenesis and uncovers a developmental mechanism, coordinated by the Ga and ephrin-B signaling pathways, for control of the balance between self-renewal and differentiation in neural progenitor cells. STEM CELLS 2010;28:1581-1589
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