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

Research output: Contribution to journalArticle

244 Citations (Scopus)

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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Glycogen Synthase Kinase 3
Homeostasis
Catenins
Wnt Signaling Pathway
Hedgehogs
Fibroblast Growth Factors
Brain
Neurons
Mutation

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

GSK-3 is a master regulator of neural progenitor homeostasis. / Kim, Woo Yang; Wang, Xinshuo; Wu, Yaohong; Doble, Bradley W.; Patel, Satish; Woodgett, James R.; Snider, William D.

In: Nature Neuroscience, Vol. 12, No. 11, 01.11.2009, p. 1390-1397.

Research output: Contribution to journalArticle

Kim, WY, Wang, X, Wu, Y, Doble, BW, Patel, S, Woodgett, JR & Snider, WD 2009, 'GSK-3 is a master regulator of neural progenitor homeostasis', Nature Neuroscience, vol. 12, no. 11, pp. 1390-1397. https://doi.org/10.1038/nn.2408
Kim WY, Wang X, Wu Y, Doble BW, Patel S, Woodgett JR et al. GSK-3 is a master regulator of neural progenitor homeostasis. Nature Neuroscience. 2009 Nov 1;12(11):1390-1397. https://doi.org/10.1038/nn.2408
Kim, Woo Yang ; Wang, Xinshuo ; Wu, Yaohong ; Doble, Bradley W. ; Patel, Satish ; Woodgett, James R. ; Snider, William D. / GSK-3 is a master regulator of neural progenitor homeostasis. In: Nature Neuroscience. 2009 ; Vol. 12, No. 11. pp. 1390-1397.
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