The mammalian musculature provides mechanical force for locomotion. This system undergoes remodeling throughout lifetime and displays remarkable ability to regenerate from reservoirs of muscle stem cells, called satellite cells. Yet, how these cells are maintained, both in their quiescent state as well as in their regenerative capacity, is largely undefined. I propose to define the role of b1-integrin in these processes by using a Pax7-Cre-ERT2 fusion gene (the Pax7CE allele) for tamoxifen (tmx) inducible gene inactivation of a conditional allele of b1-integrin (b1-integrinflox), coupled with lineage tracingto address the questions outlined in the aims below:
Aim 1 : Function of b1-integrin in the quiescent satellite cell: I will examine b1- integrin inactivated satellite cells under normal homeostasis to assess: 1) Do quiescent satellite cells require b1-integrin? 2) Does the loss of b1-integrin affect adhesion of the satellite cell to the extracellular matrix? Aim 2: Function of b1-integrin in satelite cell activation: I will use injury models to further ask: 1) Can b1-integrin null satellite cells sstain muscle regeneration? 2) Do b1- integrin null satellite cells become activated and proliferate?
Developmental studies in the mouse have implicated b1-integrin as an essential regulator of muscle integrity. I plan to use newly developed genetic tools to define the role of b1-integrin in adult muscle satellite cells (i.e. muscle stem cells) in norma and injured conditions. My research will provide understanding towards the cellular biology of satellite cells, which have the therapeutic potential to ameliorate muscular dystrophies.
|Rozo, Michelle; Li, Liangji; Fan, Chen-Ming (2016) Targeting Î²1-integrin signaling enhances regeneration in aged and dystrophic muscle in mice. Nat Med 22:889-96|