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The Journal of Neuroscience, February 11, 2009, 29(6):1874-1886; doi:10.1523/JNEUROSCI.3095-08.2009

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Development/Plasticity/Repair
Pten Deletion in Adult Neural Stem/Progenitor Cells Enhances Constitutive Neurogenesis

Caroline Gregorian,¹ Jonathan Nakashima,¹ Janel Le Belle,¹ John Ohab,² Rachel Kim,¹ Annie Liu,¹ Kate Barzan Smith,¹ Matthias Groszer,^1,3 A. Denise Garcia,⁴ Michael V. Sofroniew,⁴ S. Thomas Carmichael,² Harley I. Kornblum,^1,5 Xin Liu,^1,3 and Hong Wu¹

Departments of ¹Molecular and Medical Pharmacology, ²Neurology, ³Pathology and Laboratory Medicine, and ⁴Neurobiology, ⁵The Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095

Correspondence should be addressed to Dr. Hong Wu, Department of Molecular and Medical Pharmacology, CHS 23-214, University of California, Los Angeles School of Medicine, 650 CE Young Drive South, Los Angeles, CA 90095-1735. Email: hwu{at}mednet.ucla.edu

Here we show that conditional deletion of Pten in a subpopulation of adult neural stem cells in the subependymal zone (SEZ) leads to persistently enhanced neural stem cell self-renewal without sign of exhaustion. These Pten null SEZ-born neural stem cells and progenies can follow the endogenous migration, differentiation, and integration pathways and contribute to constitutive neurogenesis in the olfactory bulb. As a result, Pten deleted animals have increased olfactory bulb mass and enhanced olfactory function. Pten null cells in the olfactory bulb can establish normal connections with peripheral olfactory epithelium and help olfactory bulb recovery from acute damage. Following a focal stroke, Pten null progenitors give rise to greater numbers of neuroblasts that migrate to peri-infarct cortex. However, in contrast to the olfactory bulb, no significant long-term survival and integration can be observed, indicating that additional factors are necessary for long-term survival of newly born neurons after stroke. These data suggest that manipulating PTEN-controlled signaling pathways may be a useful step in facilitating endogenous neural stem/progenitor expansion for the treatment of disorders or lesions in regions associated with constitutive neurogenesis.

Key words: SEZ; PTEN; neurogenesis; olfactory; neural repair; poststroke

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Received July 3, 2008; revised Nov. 8, 2008; accepted Dec. 17, 2008.

Correspondence should be addressed to Dr. Hong Wu, Department of Molecular and Medical Pharmacology, CHS 23-214, University of California, Los Angeles School of Medicine, 650 CE Young Drive South, Los Angeles, CA 90095-1735. Email: hwu{at}mednet.ucla.edu

This article has been cited by other articles:

				C. Gregorian, J. Nakashima, S. M. Dry, P. L. Nghiemphu, K. B. Smith, Y. Ao, J. Dang, G. Lawson, I. K. Mellinghoff, P. S. Mischel, et al. PTEN dosage is essential for neurofibroma development and malignant transformation PNAS, November 17, 2009; 106(46): 19479 - 19484. [Abstract] [Full Text] [PDF]

				B. H. Dobkin Collaborative Models for Translational Neuroscience and Rehabilitation Research Neurorehabil Neural Repair, September 1, 2009; 23(7): 633 - 640. [Abstract] [PDF]

				A. Iwanami, T. F. Cloughesy, and P. S. Mischel Striking the balance between PTEN and PDK1: it all depends on the cell context Genes & Dev., August 1, 2009; 23(15): 1699 - 1704. [Abstract] [Full Text] [PDF]

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