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Originally published in Science Express on 1 November 2001
Science 7 December 2001:
Vol. 294. no. 5549, pp. 2186 - 2189
DOI: 10.1126/science.1065518
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Reports

Negative Regulation of Neural Stem/Progenitor Cell Proliferation by the Pten Tumor Suppressor Gene in Vivo

Matthias Groszer,124 Rebecca Erickson,2 Deirdre D. Scripture-Adams,5 Ralf Lesche,12* Andreas Trumpp,7 Jerome A. Zack,56 Harley I. Kornblum,23 Xin Liu,24dagger Hong Wu12dagger

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.

1 Howard Hughes Medical Institute,
2 Department of Molecular and Medical Pharmacology,
3 Department of Pediatrics,
4 Department of Pathology and Laboratory Medicine,
5 Department of Medicine and AIDS Institute,
6 Department of Microbiology and Molecular Genetics, UCLA School of Medicine, Los Angeles, CA 90095, USA.
7 Institut Suisse de Recherche Expérimentale sur le Cancer, Ch. de Boveresses 155, 1066 Epalinges/Lausanne, Switzerland.
*   Present address: Epigenomics AG, Kastanienallee 24, 10435 Berlin, Germany.

dagger    To whom correspondence should be addressed. E-mail: xliu{at}mednet.ucla.edu, hwu{at}mednet.ucla.edu

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