Open AccessWip1 Regulates the Generation of New Neural Cells in the Adult Olfactory Bulb through p53‐Dependent Cell Cycle Control
Author(s) -
Zhu YunHua,
Zhang ChengWu,
Lu Li,
Demidov Oleg N.,
Sun Li,
Yang Lan,
Bulavin Dmitry V.,
Xiao ZhiCheng
Publication year - 2009
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.65
Subject(s) - biology , olfactory bulb , neural stem cell , bulb , microbiology and biotechnology , cell cycle , olfactory system , neural cell , cell , neuroscience , stem cell , central nervous system , botany , genetics
Continual generation of new neural cells from adult neural stem/progenitor cells (NPCs) is an important component of life‐long brain plasticity. However, the intrinsic regulation of this process remains poorly defined. Here we report that Wip1 phosphatase, previously studied in oncogenesis, functions as a crucial physiological regulator in adult neural cell generation. Wip1 deficiency resulted in a 90% decrease in new cell formation in adult olfactory bulb, accompanied by aberrantly decreased NPC amplification, stem cell frequency, and self‐renewal. At a cellular level, Wip1 knockout NPCs exhibit a prolonged cell cycle, an accumulation at G 2 to M phase transition, and enhanced p53 activity. Interestingly, the impaired M‐phase entry and NPC amplification of Wip1‐null mice can be reversed in Wip1/p53 double‐null mice. Importantly, there is no difference in NPC amplification between p53‐null and Wip1/p53 double‐null mice. Our data demonstrate that Wip1 regulates the generation of new neural cells in adult olfactory bulb specifically through p53‐dependent M‐phase entry of the NPC cell cycle. S TEM C ELLS 2009;27:1433–1442