Key Investigators: Alec Smith, Cecelia Watson, Darren Player, Mark Bothwell, David Mack, Philip Barrett
Muscle spindles consist of encapsulated groups of specialized skeletal muscle fiber subtypes (bag and chain intrafusal fibers), embedded within skeletal muscle, which function as proprioceptive sensory end organs. They receive innervation by motor neurons and proprioceptive sensory neurons to create functional reflex circuits. Their normal function and dysfunction in disease has been insufficiently studied, because their sparse distribution in muscle hinders their study. We are producing muscle spindle cells in vitro by differentiation of human induced pluripotent stem cells and developing methods to achieve innervation by iPSC-derived sensory and motor neurons. We are investigating whether muscle spindle dysfunction causes discoordination in muscular dystrophies, and whether distal arthrogryposis caused by MYH3 mutations results from muscle spindle dysfunction.