The role of p107 in skeletal muscle adaption: Understanding progenitor cell differentiation into muscle fiber

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The fiber characteristics in skeletal muscle control how the muscle will function. In the mouse, used as a model for human physiology, the muscle fiber types are generally classified according to four major forms. These forms display differences with respect to their metabolic potential, i.e. how much and what type of food energy will be consumed. The fibers consist of slow oxidative types, that are the primary muscle type of an endurance athlete and fast glycolytic types that are the predominate muscle type of athletes using quick bursts of energy, such as sprinters. In response to physiological pressures such as exercise and diet, adult skeletal muscle can switch fiber types. Currently, it is not known how the muscle stem cells lead to specific fiber types. Our research program is involved in finding how and why the muscle stem cells become determined to a fast or slow fiber type fate. Our recent published results show that a protein called p107 plays a role in determining the fiber type character of skeletal muscle. We had demonstrated that mice that do not possess p107 have higher levels of slow type muscle fibers. Our results therefore indicate a central role for p107 in determining the metabolic state of skeletal muscle by controlling what fiber types will be made. Our research program addresses how p107 controls the stem cells to produce the fast fiber types over the slower ones. This will be accomplished by three different approaches. 1) We will determine the molecular role of p107 in muscle fiber type commitment, 2) We will discover the p107 interacting partners during fiber type formation and 3) we will find how p107 behaves during exercise. Our research will provide important insight into how p107 controls stem cells to make specific fiber types.