Gli3 is required for the establishment of adult SVZ neural stem cell niche and postnatal olfactory neurogenesis via interaction with Notch pathway

Tuesday, October 25, 2011 — Poster Session II
Noon – 2:00 p.m.	Natcher Conference Center	NICHD	STEMCELL-8

Authors

• H Wang
• A Kane
• E Karey
• C Lee
• S Ahn

Abstract

Positive Shh signaling via Gli transcription activators is required for the adult neural stem cells (NSCs) in the subventricular zone (SVZ) neurogenic niche, while the role of Shh negative signaling via Gli transcription repressor (Gli3) has not been investigated. In this study, we conditionally removed Gli3 in radial glial cells (RGCs; the origin of both NSCs and ependymal cells) during embryonic development, in differentiated ependymal cells, or in NSCs in the postnatal SVZ using Nestin-Cre (NC), FoxJ1-Cre (FC), and GFAP-Cre (GC) mouse lines, respectively. We found that the NC;Gli3cko and FC;Gli3cko mice displayed defective SVZ cytoarchitecture and reduced olfactory neurogenesis. Together with our observation that the ependymal cells do not respond to Shh positive signaling, our mutant analysis indicates that Gli3 mainly functions in the ependymal cells as a repressor of Shh signaling. When Gli3 level was directly manipulated using in vivo electroporation, the genetic phenotypes were recapitulated. Finally, we found that the components of Notch signaling pathway were differentially changed in the Gli3cko mice. Taken together, our results suggest that the establishment and maintenance of SVZ neurogenic niche require Shh negative signaling via Gli3 repressor to regulate Notch-based ependymal and NSC interaction.

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