Abstract

Adult neurogenesis occurs in two distinct regions inside the brain, the subventricular zone (SVZ) in the lateral ventricle and the subgranular zone (SGZ) of the dentate gyrus in hippocampus. Neural stem cells (NSCs) are controlled by several intrinsic and extrinsic factors that regulate their proliferation, survival and differentiation in the adult hippocampus. REST/NRSF is considered a master transcription factor that regulates hundreds of neuronal genes essential for neuronal fate decision. In this study, we address the role of REST/NRSF (RE1 silencing transcription factor/Neuro-restrictive silencer factor) in regulating adult neurogenesis in hippocampus.REST/NRSF has biphasic expression in neural stem cells and mature neurons. It serves as a critical controller of neural stem cell fate transition and neuronal differentiation.REST/NRSF maintains neural stem cell quiescence preventing its precocious differentiation into neurons. This study shows that deregulation of REST/NRSF function, conditional deletion in REST/NRSF allele, in vivo leads to a transient increase in adult hippocampal neurogenesis and NSCs exit quiescence. Consequently, this reflects a decrease in newborn neurons due to stem cell pool exhaustion. Our work asserts on the critical role of REST/NRSF as a negative master regulator for adult neurogenesis. The results offer a new horizon for the role of NRSF in regenerative medicine and development of new treatment strategies for cancer research.

Department

Biotechnology Program

Degree Name

MS in Biotechnology

Date of Award

2-1-2011

Online Submission Date

January 2011

First Advisor

Azzazy, Hassan

Second Advisor

Hsieh, Jenny

Document Type

Thesis

Extent

NA

Library of Congress Subject Heading 1

Transcription factors.

Library of Congress Subject Heading 2

Hematopoietic stem cells -- Genetic aspects.

Rights

The author retains all rights with regard to copyright. The author certifies that written permission from the owner(s) of third-party copyrighted matter included in the thesis, dissertation, paper, or record of study has been obtained. The author further certifies that IRB approval has been obtained for this thesis, or that IRB approval is not necessary for this thesis. Insofar as this thesis, dissertation, paper, or record of study is an educational record as defined in the Family Educational Rights and Privacy Act (FERPA) (20 USC 1232g), the author has granted consent to disclosure of it to anyone who requests a copy.

IRB

Not necessary for this item

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