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A SPECIFIC REQUIREMENT FOR FLOORPLATE SHH IN SPINAL CORD DEVELOPMENT

by
Kwanha Yu
B.S., Rensselaer Polytechnic Institute 2006


Thesis Advisor: Michael P Matise, Ph.D.
Graduate Program in Cell & Developmental Biologuy


RWJMS Research Tower
Room V-10
Piscataway

Wednesday, December 12, 2012
10:00 a.m.


Abstract

Sonic Hedgehog (Shh) is a secreted protein that plays a critical role in the development of the central nervous system. In the spinal cord, there are two tissue sources of Shh: the notochord (ShhNOTO) and the floor plate (ShhFP). Although prior studies have shown a critical role for Shh in patterned gene expression, the individual requirements of each Shh source have not been clearly defined. To address this, this study employed conditional mutagenesis in mice to selectively inactivate ShhFP while preserving ShhNOTO. To disrupt the signal transduction pathway at both the ligand and receptor levels, Smo was also inactivated in neural tube progenitors, an approach complementing the conditional inactivation of Shh. During early neural tube development, we found progenitor gene expression and patterning remained relatively unchanged suggesting a stronger reliance on ShhNOTO, which supports prior studies. However during gliogenesis, ShhFP is required in specifying ventrally derived oligodendrocyte cell fates, specifically via repression of Gli3 repressors in progenitors. Yet, despite the decrease in oligodendrocytes, it appears that oligodendrocytes eventually recover to wild type levels in post natal tissues. Interestingly, our study also found a role for Shh signaling in the expression of astroctye associated genes, raising the possibility of a link between Hh signaling and astrocyte development. Finally, we also found during late embryogenesis, hedgehog signaling is required for the proper maintenance of the spinal cord ventricular zone and the eventual formation of the adult ependymal zone. Taken together, the results demonstrate a specific and critical requirement for ShhFP in regulating the specification and differentiation of glial and ependymal cells in the spinal cord.


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