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FRIMEDBIO-Fri prosj.st. med.,helse,biol

Neil3, a novel function for self-renewal and proliferation of neural progenitor cells

Awarded: NOK 3.8 mill.

The major cell types comprising the mammalian central nervous system arise from neural stem cells (NSC) and progenitor cells (NPC), including neurons, astrocytes and oligodendrocytes. In this proposal we aim to characterize a novel gene function, Neil3, r equired for neural stem/progenitor cell maintenance and proliferation. Neil3 is a structural homologue of a conserved family of DNA glycosylases in mammalian cells. In brain of newborn rats and mice mNeil3 is transcribed only in the subventricular zone an d the rostro migratory stream, which contains most of the NSC in brain. Moreover the pool of neural stem/progenitor cells in neil3 knock-out animals is strongly impaired. Hypoxic-ischemic brain injury showed significant increase in neuronal tissue loss in brain of the neil3 deficient mouse as compared to the wt. It thus appears that Neil3 has evolved a novel function unlike other DNA glycosylases in brain. We propose that Neil3 contribute to the self-renewing capability that characterizes NPC and NSC. The overall aim of the proposed project is to unravel the biochemical features of Neil3 and to further explore the role of Neil3 in NSC/NPC and the transition of NSC/NPC towards a neuronal faith.

Funding scheme:

FRIMEDBIO-Fri prosj.st. med.,helse,biol