Vanderluit, Jacqueline L. and Ferguson, Kerry L. and Nikoletopoulou, Vassiliki and Parker, Maura and Ruzhynsky, Vladimir A. and Alexson, Tania and McNamara, Stephen M. and Park, David S. and Rudnicki, Michael and Slack, Ruth S. (2004) p107 regulates neural precursor cells in the mammalian brain. Journal of Cell Biology, 166 (6). pp. 853-863.
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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.
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|Keywords:||Neural stem cells, Self-renewing division, Regeneration|
|Department(s):||Medicine, Faculty of|
|Date:||14 September 2004|
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