p107 regulates neural precursor cells in the mammalian brain

J Cell Biol. 2004 Sep 13;166(6):853-63. doi: 10.1083/jcb.200403156. Epub 2004 Sep 7.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Apoptosis
  • Blotting, Western
  • Brain / cytology*
  • Bromodeoxyuridine / metabolism
  • Cell Division
  • Cells, Cultured
  • Gene Expression Regulation, Developmental*
  • Immunohistochemistry
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Neurons / metabolism*
  • Olfactory Bulb / cytology
  • RNA, Messenger / metabolism
  • Receptors, Notch
  • Retinoblastoma Protein / genetics*
  • Stem Cells / metabolism*

Substances

  • Membrane Proteins
  • RNA, Messenger
  • Receptors, Notch
  • Retinoblastoma Protein
  • Bromodeoxyuridine