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.
|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|