Poster Sessions

DEV-7

Hui Wang

H. Wang, G. Ge, S. Ahn

Conditional Gli3 Mutant Reveals Its Specific Role in Mouse Cortical Development via Affecting the Intermediate Progenitors

Components of Hedgehog (Hh) signaling pathway are widely involved in embryonic development. The role of Gli3, the major negative regulator of Hh pathway, in cortical development especially on the regulation of neural stem/progenitor cells, is largely unknown. In this study, we removed Gli3 pan-neuronaly using Nestin-Cre (NC) mice. The conditional Gli3 mutant mice (NC; Gli3c/-) survive up to postnatal 4 weeks unlike the null mutants that die at birth. We found that the proliferation in the ventricular zone (VZ) is reduced and cell cycle exit is increased at E16.5 in the mutants. As a result, the intermediate progenitors (IPs) are almost gone at E18.5, which leads to the dramatic decrease of superficial layer cortical neurons postnatally. Interestingly, we observed that more GFAP+ cells are found in the ventricular walls in the postnatal mutants and EM study further demonstrated the disruption of ependymal wall integrity and SVZ cyto-architecture. This is the first study focusing on Gli3 function in mammalian cortical development using conditional gene targeting and this study indicates that Gli3 plays an essential role in regulating IPs and superficial layer neuronal development. Acknowledgement: NIH intramural research grant