All ETDs from UAB

Advisory Committee Chair

Rosa A Serra

Advisory Committee Members

Bradly K Yoder

Chengbei Chang

Guillermo Marques

Joanne Murphy-Ullrich

Document Type

Dissertation

Date of Award

2008

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

skeletal element is essential for body movement along with the joints, muscles, tendons and ligaments. They also protect internal organs and serve as a reservoir for hematopoietic stem cells and minerals. To accomplish these multiple tasks, the size and shape of the skeletal elements need to be carefully designed during development of the embryo. Skeletal formation in vertebrae is a complex developmental processes controlled by dynamic and well-balanced interactions between a number of molecular signals. Intensive efforts in the past several decades have made substantial progress in understanding molecular and cellular mechanisms of skeletal development. Despite the fact that TGFß signaling has been considered as a potential trigger for the onset of skeletal development, it has not been studied well. Here, we show important roles for TGFß signaling in skeletal development using a transgenic mouse model in which Tgfbr2 is specifically deleted in cells that will be programmed to become various components of the skeleton. Primarily, discoveries in this study show the precise role of TGFß signaling in specific stages of skeletal development. Defining the role of TGFß signaling in specific stages, cells or tissues has been difficult because of the complexity of skeletal development. Secondly, results presented here provide a novel function of TGFß signaling in skeletal development, which has not been previously suggested. Finally, evidence provided in this study shows multiple roles of TGFß in intramembranous and endochondral bone formation.

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