Neural stem cells (NSCs) are a multipotent cell population capable of both self-renewal and differentiation into neurons and glia. Engraftment of NSCs has been proposed as a therapeutic approach for a variety of human neurological disorders, however, genetic control of the production, potency and capacity for renewal of this cell population are not fully understood. This proposal is based on unexpected observations in the PI's laboratory that deletion of a particular zinc finger protein impairs the propagation of NSCs from forebrain subventricular zone, both in vivo and in vitro.
The aims of this proposal will test the hypotheses (1) that this transcriptional regulator controls self renewal and potency of NSCs and multipotent progenitors;(2) that absence of this factor results in premature differentiation at the expense of renewal;and (3) that this factor acts by titrating the availability of differentiation-promoting transcriptional regulators through the formation of heteromeric complexes in the absence of differentiation signals.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS060109-04
Application #
7991840
Study Section
Special Emphasis Panel (ZRG1-GTIE-A (01))
Program Officer
Owens, David F
Project Start
2007-12-15
Project End
2012-11-30
Budget Start
2010-12-01
Budget End
2011-11-30
Support Year
4
Fiscal Year
2011
Total Cost
$331,209
Indirect Cost
Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Cho, Young-Wook; Hong, Chen-Jei; Hou, Aiju et al. (2013) Zfp423 binds autoregulatory sites in p19 cell culture model. PLoS One 8:e66514
Chaki, Moumita; Airik, Rannar; Ghosh, Amiya K et al. (2012) Exome capture reveals ZNF423 and CEP164 mutations, linking renal ciliopathies to DNA damage response signaling. Cell 150:533-48