Negative regulation of neural stem/progenitor cell proliferation by the Pten tumor suppressor gene in vivo

The mechanisms controlling neural stem cell proliferation are poorly unders tood. Here we demonstrate that the PTEN tumor suppressor plays an important role in regulating neural stem/progenitor cells in vivo and in vitro. Mice lacking PTEN exhibited enlarged, histoarchitecturally abnormal brains, whi ch resulted from increased cell proliferation, decreased cell death, and en larged cell size. Neurosphere cultures revealed a greater proliferation cap acity for tripotent Pten(-/-) central nervous system stem/progenitor cells, which can be attributed, at Least in part, to a shortened cell cycle. Howe ver, cell fate commitments of the progenitors were largely undisturbed. Our results suggest that PTEN negatively regulates neural stem cell proliferat ion.