All ETDs from UAB

Advisory Committee Chair

Rosa Serra

Advisory Committee Members

Susan Bellis

Chenbei Chang

Amjad Javed

Ho-Wook Jun

Document Type

Dissertation

Date of Award

2013

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

The intervertebral disc (IVD) is a fibrocartilaginous tissue that acts as a shock absorber between adjacent vertebrae in the spinal column. It is comprised of two parts, the inner jelly-like nucleus pulposus (NP) and the outer more fibrous annulus fibrosus (AF). Most IVD research has focused on the development of the NP, which is derived from condensations of the notochord involving sonic hedgehog (Shh) signaling. In contrast, very little is known about the molecular mechanisms underlying the specific development of the AF of the IVD. The AF is derived from the sclerotome, which is formed by the ventral half of the somites. It is yet to be determined what genes control this differentiation into IVD. The transforming growth factor-ß (TGF-ß) signaling pathway is important for various aspects of development. One of these developmental processes is the formation of the AF of the IVD. Our previous studies show that conditionally deleting the Tgf-ß type II receptor (Tgfbr2) from type II collagen-expressing cells in mice, results in defective IVD development.This leads us to believe that TGF-ß is involved in IVD development as well as its long-term maintenance. To elucidate the mechanism of action, we used microarrays to determine what genes were expressed in the IVD during development as well as which genes were dys-regulated by the deletion of TGF-ß signaling in vivo or the addition of TGF-ß in vitro. We confirmed the expression of many of these genes in the IVD and selected transcription factors for further study, including avian erythroblastosis virus E-26 (v-ets) oncogene related (ERG). While ERG was able to suppress markers of the vertebral body, it was unable to increase IVD markers by itself. However, in the presence of TGF-ß1, ERG appears to be able to enhance the effect of TGF-ß on IVD markers. This suggests that TGF-ß may be acting to suppress the development of neighboring vertebral bodies, as well as induce the development of the AF through induction of ERG.

Share

COinS