News archives


OCTOBER - DECEMBER 17

JULY - SEPTEMBER 17

APRIL - JUNE 17

JANUARY - MARCH 17

OCTOBER - DECEMBER 16

JULY - SEPTEMBER 16

APRIL - JUNE 16

JANUARY - MARCH 16

OCTOBER - DECEMBER 15

JULY - SEPTEMBER 15

APRIL - JUNE 15

JANUARY - MARCH 15

OCTOBER - DECEMBER 14

JULY - SEPTEMBER 14

APRIL - JUNE 14

JANUARY - MARCH 14

OCTOBER - DECEMBER 13

JULY - SEPTEMBER 13

APRIL - JUNE 13

JANUARY - MARCH 13

OCTOBER - DECEMBER 12

JULY - SEPTEMBER 12

APRIL - JUNE 12

JANUARY - MARCH 12

OCTOBER - DECEMBER 11

JULY - SEPTEMBER 11

APRIL - JUNE 11

JANUARY - MARCH 11

OCTOBER - DECEMBER 10

JULY - SEPTEMBER 10

APRIL - JUNE 10

JANUARY - MARCH 10

OCTOBER - DECEMBER 09

JULY - SEPTEMBER 09

APRIL - JUNE 09

JANUARY - MARCH 09

OCTOBER - DECEMBER 08

JULY - SEPTEMBER 08

APRIL - JUNE 08

JANUARY - MARCH 08

OCTOBER - DECEMBER 07

JULY - SEPTEMBER 07

APRIL - JUNE 07

JANUARY - MARCH 07

 
  current news   Press   selected story    
     
  11 May 2010  
  Congratulations to IMCBís recent PhD graduate
 
 



PhD Gradute: ZHU Yunhua
Thesis Title: Wip1 regulates proliferation of adult neural progenitors through p53-dependent G2 phase cell cycle control

Abstract
The activity of Neural Stem/Progenitor Cells (NPCs) declines with aging, however the intrinsic regulators of this process are poorly defined. Here we report that Wip1 phosphatase functions as a critical physiological regulator of adult neurogenesis and potentially operates as an important mechanism of aging-induced decline in proliferation of NPCs.

In adult olfactory bulb, a Wip1 deficiency results in a 90% decrease in new cells formation, accompanied by decreased amplification of NPCs of sub-ventricular zone, reduced stem cell frequency and self-renewal. Similarly, adult neurogenesis in hippocampus is also diminished upon knocking out Wip1. At cellular level, Wip1 deficient NPCs exhibit a prolonged cell cycle, an accumulation at G2 to M phase and elevated expression of G2 phase inhibitors. The impaired M-phase entry and reduced proliferation of Wip1 deficient NPCs are both reversed in Wip1/p53 double deficient mice. The functional rescue in a p53 deficient background was also observed in vivo in the number of NPCs and neuroblasts. Thus, Wip1 regulates the generation of new neural cells in adult olfactory bulb through a p53-dependent control of cell cycle progression.

In turn, during aging, the number of NPCs was reduced, which correlated with a marked down-regulation of Wip1 and a drastic up-regulation of p53 phosphorylation. Our results propose the important function of Wip1/p53 pathway in adult neurogenesis with possibly of regulation of NPCs aging.

Ref: Wip1 regulates the generation of new neural cells in the adult olfactory bulb through p53-dependent cell cycle control. Stem Cells. 2009 Jun;27(6):1433-42.PMID: 19489034 .


Figure Legend:
Key Data:
A: Proliferation of neural progenitors decreases during aging
B:
Complete reduction (ko) of Wip1 cause reduction in the proliferation of neural progenitors
C:
Wip1 expression reduces during aging of neural progenitors
D:
Transgenic expression of Wip1 in aged NPC promotes proliferation

Working Model:
E:
In young neural progenitors, Wip1 is abundantly expressed and represses the activity of p53 to promote cell cycle progress.
F: In old animals, expression of Wip1 is reduced, at the same time, positive regulation by accumulated DNA damage and telomere shortening increases. Therefore p53 activity rises to a high level. The activation of p53, together with the rise of p16Ink4a, restricts cell cycle progression, self-renewal as well as neuronal differentiation.

For more information on Dmitry BULAVINís Lab, please click here.