First Author | Vanderluit JL | Year | 2004 |
Journal | J Cell Biol | Volume | 166 |
Issue | 6 | Pages | 853-63 |
PubMed ID | 15353549 | Mgi Jnum | J:92520 |
Mgi Id | MGI:3053258 | Doi | 10.1083/jcb.200403156 |
Citation | Vanderluit JL, et al. (2004) p107 regulates neural precursor cells in the mammalian brain. J Cell Biol 166(6):853-63 |
abstractText | 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. |