GSK-3 is a master regulator of neural progenitor homeostasis

Woo Yang Kim, Xinshuo Wang, Yaohong Wu, Bradley W. Doble, Satish Patel, James R. Woodgett, William D. Snider

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Abstract

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 α and β 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 β-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.

Original languageEnglish (US)
Pages (from-to)1390-1397
Number of pages8
JournalNature Neuroscience
Volume12
Issue number11
DOIs
StatePublished - Nov 1 2009

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Kim, W. Y., Wang, X., Wu, Y., Doble, B. W., Patel, S., Woodgett, J. R., & Snider, W. D. (2009). GSK-3 is a master regulator of neural progenitor homeostasis. Nature Neuroscience, 12(11), 1390-1397. https://doi.org/10.1038/nn.2408