RECEPTOR TYROSINE KINASE SPECIFIC FOR THE SKELETAL-MUSCLE LINEAGE - EXPRESSION IN EMBRYONIC MUSCLE, AT THE NEUROMUSCULAR-JUNCTION, AND AFTER INJURY

While a number of growth factors have been described that are highly s pecific for particular cell lineages, neither a factor nor a receptor uniquely specific to the skeletal muscle lineage has previously been d escribed. Here we identify a receptor tyrosine kinase (RTK) specific t o skeletal muscle, which we term ''MuSK'' for muscle-specific kinase. MuSK is expressed at low levels in proliferating myoblasts and is indu ced upon differentiation and fusion, In the embryo, it is specifically expressed in early myotomes and developing muscle. MUSK is then drama tically down-regulated in mature muscle, where it remains prominent on ly at the neuromuscular junction; MuSK is thus the only known RTK that localizes to the neuromuscular junction. Strikingly, MuSK expression is dramatically induced throughout the adult myofiber after denervatio n, block of electrical activity, or physical immobilization. In humans , MuSK maps to chromosome 9q31.3-32, which overlaps with the region re ported to contain the Fukuyama muscular dystrophy mutation. Identifica tion of MUSK introduces a novel receptor-factor system that seems sure to play an important and selective role in many aspects of skeletal m uscle development and function.