Pten deletion in adult neural stem/progenitor cells enhances constitutive neurogenesis.
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.
Gregorian
Caroline
C
Department of Molecular and Medical Pharmacology, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA.
Nakashima
Jonathan
J
Le Belle
Janel
J
Ohab
John
J
Kim
Rachel
R
Liu
Annie
A
Smith
Kate Barzan
KB
Groszer
Matthias
M
Garcia
A Denise
AD
Sofroniew
Michael V
MV
Carmichael
S Thomas
ST
Kornblum
Harley I
HI
Liu
Xin
X
Wu
Hong
H
D000367:Age Factors; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D017353:Gene Deletion; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009423:Nervous System Neoplasms / Q000201:enzymology / Q000235:genetics; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000201:enzymology / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics; D012903:Smell / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000201:enzymology / Q000502:physiology*
D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse