PTEN in neural precursor cells: regulation of migration, apoptosis, and proliferation

Mol Cell Neurosci. 2002 May;20(1):21-9. doi: 10.1006/mcne.2002.1115.

Abstract

PTEN is a lipid phosphatase, and PTEN mutations are associated with gliomas, macrocephaly, and mental deficiencies. We have used PTEN +/- mice to assess PTEN's role in subventricular zone (SVZ) precursor cells. For cultured SVZ neurosphere cells, haploinsufficiency for PTEN increases phosphorylation of Akt and forkhead transcription factor and slightly enhances proliferation. Based on a filter penetration assay, PTEN +/- cells are substantially more migratory and invasive than +/+ cells. The +/- cells also are more resistant to H(2)O(2)-induced apoptosis. Analysis of PTEN +/- and +/+ mice by BrdU labeling reveals no difference in the rate of cell proliferation in the SVZ. Exit of BrdU-labeled cells from the SVZ and radial migration to the outer layers of the olfactory bulb are more rapid for +/- cells. These observations indicate that PTEN regulates SVZ precursor cell function and is particularly important for migration and apoptosis in response to oxidative stress.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Brain / cytology
  • Brain / growth & development*
  • Brain / metabolism*
  • Bromodeoxyuridine
  • Cell Count
  • Cell Division / physiology*
  • Cell Movement / physiology*
  • Cerebral Ventricles / cytology
  • Cerebral Ventricles / growth & development
  • Cerebral Ventricles / metabolism
  • Female
  • Forkhead Transcription Factors
  • Male
  • Mice
  • Mice, Knockout
  • Neurons / cytology
  • Neurons / metabolism*
  • Olfactory Bulb / cytology
  • Olfactory Bulb / growth & development
  • Olfactory Bulb / metabolism
  • Oxidative Stress / physiology
  • PTEN Phosphohydrolase
  • Phosphatidylinositol Phosphates / metabolism
  • Phosphoric Monoester Hydrolases / deficiency*
  • Phosphoric Monoester Hydrolases / genetics
  • Protein Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-akt
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Transcription Factors / metabolism
  • Tumor Suppressor Proteins / deficiency*
  • Tumor Suppressor Proteins / genetics

Substances

  • Forkhead Transcription Factors
  • Foxf1 protein, mouse
  • Phosphatidylinositol Phosphates
  • Proto-Oncogene Proteins
  • Transcription Factors
  • Tumor Suppressor Proteins
  • phosphatidylinositol 3,4,5-triphosphate
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Phosphoric Monoester Hydrolases
  • PTEN Phosphohydrolase
  • Bromodeoxyuridine