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Publication : GSK-3 is a master regulator of neural progenitor homeostasis.

First Author  Kim WY Year  2009
Journal  Nat Neurosci Volume  12
Issue  11 Pages  1390-7
PubMed ID  19801986 Mgi Jnum  J:154623
Mgi Id  MGI:4397633 Doi  10.1038/nn.2408
Citation  Kim WY, et al. (2009) GSK-3 is a master regulator of neural progenitor homeostasis. Nat Neurosci 12(11):1390-7
abstractText  The development of the brain requires the exquisite coordination of progenitor proliferation and differentiation to achieve complex circuit assembly. It has been suggested that glycogen synthase kinase 3 (GSK-3) acts as an integrating molecule for multiple proliferation and differentiation signals because of its essential role in the RTK, Wnt and Shh signaling pathways. We created conditional mutations that deleted both the alpha and beta forms of GSK-3 in mouse neural progenitors. GSK-3 deletion resulted in massive hyperproliferation of neural progenitors along the entire neuraxis. Generation of both intermediate neural progenitors and postmitotic neurons was markedly suppressed. These effects were associated with the dysregulation of beta-catenin, Sonic Hedgehog, Notch and fibroblast growth factor signaling. Our results indicate that GSK-3 signaling is an essential mediator of homeostatic controls that regulate neural progenitors during mammalian brain development.
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