Negative regulators of Shh and Notch pathways interact to establish the neural stem cell niche

Thursday, October 11, 2012 — Poster Session IV
2:00 p.m. – 4:00 p.m.	Natcher Conference Center, Building 45	NICHD	STEMCELL-7

Authors

• H Wang
• A
• W Kane
• E Karey
• C Lee
• Y Zhang
• M
• J Holtzman
• S Ahn

Abstract

Neural stem cells (NSCs) reside in neurogenic niches and continuously produce new neurons. While niche cells provide environmental cues that regulate adult neurogenesis, how distinct niche cells are produced remains unclear. We first show that Gli3 repressor (Gli3R), a negative regulator of Shh pathway, is critical for establishment and maintenance of the neurogenic niche. We demonstrate that embryonic radial glia require Gli3R to correctly specify postnatal ependymal cells and NSCs. We also found that proper neurogenesis depends on the continuous presence of Gli3R in ependymal cells, but not NSCs. Finally, we provide in vivo evidence that Gli3R maintains Numb, a negative regulator of the Notch pathway, in ependymal cells to influence neurogenic activity of neighboring NSCs. Our findings highlight the importance of the restricted expression of negative regulators of Shh and Notch pathways (Gli3R and Numb, respectively) and provide a better understanding of the interplay between NSCs and environment.

back to top