Journal
SCIENCE
Volume 294, Issue 5549, Pages 2186-2189Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1065518
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Funding
- NICHD NIH HHS [U54 HD087101] Funding Source: Medline
- NIMH NIH HHS [MH062800-01] Funding Source: Medline
- NINDS NIH HHS [NS38489] Funding Source: Medline
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The mechanisms controlling neural stem cell proliferation are poorly understood. 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, which resulted from increased cell proliferation, decreased cell death, and enlarged cell size. Neurosphere cultures revealed a greater proliferation capacity for tripotent Pten(-/-) central nervous system stem/progenitor cells, which can be attributed, at Least in part, to a shortened cell cycle. However, cell fate commitments of the progenitors were largely undisturbed. Our results suggest that PTEN negatively regulates neural stem cell proliferation.
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