Wip1 regulates the generation of new neural cells in the adult olfactory bulb through p53-dependent cell cycle control

Yun-Hua Zhu, Cheng-Wu Zhang, Li Lu, Oleg N Demidov, Li Sun, Lan Yang, Dmitry V Bulavin, Zhi-Cheng Xiao

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44 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)1433 - 1442
Number of pages10
JournalStem Cells
Volume27
Issue number6
DOIs
Publication statusPublished - 2009
Externally publishedYes

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