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Published online 7 September 2004. doi:10.1083/jcb.200403156
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 166, Number 6, 853-863
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Article

 p107 regulates neural precursor cells in the mammalian brain

Jacqueline L. Vanderluit1, Kerry L. Ferguson1, Vassiliki Nikoletopoulou1, Maura Parker3, Vladimir Ruzhynsky1, Tania Alexson2, Stephen M. McNamara1, David S. Park1, Michael Rudnicki3, and Ruth S. Slack1

1 Neuroscience Research Group, Ottawa Health Research Institute, Ottawa, Ontario, Canada K1H 8M5
2 Neurobiology Research Group, Department of Anatomy and Cell Biology, University of Toronto, Toronto, Ontario, Canada M5S 1A8
3 Molecular Medicine Program, Ottawa Health Research Institute, Ottawa, Ontario, Canada, K1H 8L6

Address correspondence to Dr. Ruth S. Slack, Neuroscience Research Group, Ottawa Health Research Institute, 451 Smyth Rd., Ottawa, ON, K1H 8M5. Tel.: (613) 562-5800, ext. 8458. Fax: (613) 562-5403. email: rslack{at}uottawa.ca

Here we show a novel function for Retinoblastoma family member, p107 in controlling stem cell expansion in the mammalian brain. Adult p107-null mice had elevated numbers of proliferating progenitor cells in their lateral ventricles. In vitro neurosphere assays revealed striking increases in the number of neurosphere forming cells from p107–/– brains that exhibited enhanced capacity for self-renewal. An expanded stem cell population in p107-deficient mice was shown in vivo by (a) increased numbers of slowly cycling cells in the lateral ventricles; and (b) accelerated rates of neural precursor repopulation after progenitor ablation. Notch1 was up-regulated in p107–/– neurospheres in vitro and brains in vivo. Chromatin immunoprecipitation and p107 overexpression suggest that p107 may modulate the Notch1 pathway. These results demonstrate a novel function for p107 that is distinct from Rb, which is to negatively regulate the number of neural stem cells in the developing and adult brain.

Key Words: neural stem cells, self-renewing division, regeneration

Abbreviations used in this paper: CNS, central nervous system; Rb, retinoblastoma.


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