Date of Award

Fall 2014

Degree Type


Degree Name

Doctor of Philosophy (PhD)


Animal Science

First Advisor

Shihuan Kuang

Committee Chair

Shihuan Kuang

Committee Member 1

Paul Collodi

Committee Member 2

Ourania Andrisani

Committee Member 3

Xiaoqi Liu

Committee Member 4

Ryan Cabot


Skeletal muscle regeneration provides a powerful model to study the cellular and molecular mechanism governing stem cell function since the whole process is mediated by a population of muscle-resident stem cells called satellite cells. The overall aim of this dissertation is to explore the roles of Notch signaling and a novel gene (Bex1) in satellite cell function and skeletal muscle regeneration. ^ The first part of this thesis is to examine how the Notch signaling pathway regulates the satellite cell self-renewal in a disease model. The MDX mouse is a well-established model for Duchenne muscular dystrophy (DMD) and characterized by progressive muscle degeneration and regeneration. Here, I showed that the number and activity of satellite cells in MDX mice were reduced in an age-dependent manner. Given that satellite cells can self-renew to maintain the homeostasis, I further demonstrated that the self-renewal capacity was defective in MDX mice. As the Notch signaling pathway has been reported to regulate satellite cell quiescence, I continued to confirmed that the self-renewal defect was due to the perturbed Notch in MDX satellite cells. Furthermore, I attempted to genetically activate the Notch signaling pathway in satellite cells to improve muscle regeneration in MDX mice. Surprisingly, although the Notch activation increased the satellite cell number and rescued the self-renewal defects, it did not contribute to muscle regeneration. Nevertheless, this study extends our understanding of the Notch signaling pathway in the activity of satellite cells and in muscle regeneration. ^ The second part of this dissertation focuses on the roles of Bex1 in muscle regeneration. Bex1 is a novel gene with unknown functions in skeletal muscles. I first found that Bex1 was temporarily expressed in myogenic cells with a nuclear-cytoplasmic trafficking pattern during embryonic development and postnatal regeneration. The exclusive expression of Bex1 in differentiated myocytes suggests that Bex1 may play unknown roles in regulating myogenic differentiation. Previous studies suggested that Bex1 could regulate neuron cell cycle withdrawal. Here I demonstrated that Bex1 participated in myogenic differentiation independent of the cell cycle withdrawal. Instead, I showed that Bex1 promoted myoblast-myotube fusion in vitro and the regulation was independent of myogenic differentiation per se. However, Bex1 knockout mice appeared normal and did not exhibit obvious defects in the skeletal muscle. This study characterized the novel function of Bex1 in the myogenesis and facilitated the understanding of myoblast fusion process. ^ Collectively, the findings about how Notch signaling and Bex1 regulate the function of satellite cells as well as muscle regeneration derived from this dissertation will extend our understanding of the cellular and molecular mechanism of muscle regeneration. Consequently, this dissertation can shed light on providing therapeutic avenues for the prevention and treatment of muscle diseases.