The nervous system develops through the highly regulated process of proliferation and differentiation of neural stem cells. Two major regulatory pathways that maintain neural stem cells in a proliferative state or promote their differentiation are the Notch and BMP signaling pathways, respectively. In this dissertation, we demonstrate that HeyL, a member of the Hes and Hey family of Notch target genes that typically inhibit neuronal lineage commitment by neural progenitor cells exerts the opposite effect of promoting neural progenitor cells to differentiate into neurons both in vitro and in vivo. Further, our results suggest that these actions are mediated at least in part by inhibition of expression and action of other Hes and Hey factors and by activation of the proneural factor Ngn2. We also show that HeyL is activated by BMP signaling through Bmpr1a receptor. However, both Bmpr1a and Bmpr1b can promote neuronal differentiation of neural stem cells during the peak period of neurogenesis. Finally, we examine a human neural tube defect in which cerebellar growth and development is highly deficient, and we show genetic linkage to a region near PAX3, a BMP and Notch regulated gene that is involved in cerebellar neurogenesis. Collectively these results signify the importance of Notch and BMP signaling pathways and their interactions in the development of the nervous system

Last modified

• 08/07/2018

Creator

• Ali Jalali

DOI

• https://doi.org/10.21985/N2XM84

Subject

• Neuroscience Institute Graduate Program

Keyword

• Notch
• ,BMP
• Heyl
• Dandy-Walker
• PAX3
• Cephalocele

Date created

• 2007-10-11

Resource type

• Dissertation

Rights statement

• In Copyright