Skeletal muscle generates contractile forces that allow the body to execute movements for walking, speaking and breathing. Although we understand a great deal about the steps of muscle formation, the mechanisms that control muscle size are poorly understood. Even less is known about how muscles interact with skeletal elements, including connective tissue, tendon and bone. This dissertation describes a novel role for Abelson tyrosine-protein kinase 2, a non-receptor tyrosine kinase, during muscle development. First, I characterize the defects in skeletal muscle of abl2 mutant mice and show that muscle fibers in the diaphragm and other muscles are extraordinarily long in abl2 mutant mice. As a consequence of expansion of the diaphragm muscle, the central tendon of the diaphragm is proportionally reduced in size. Second, I demonstrate that abl2 controls muscle size by regulating myoblast proliferation. Third, I show that Abl2 acts in myoblasts to attenuate their proliferation, thereby limiting myoblast fusion and muscle fiber size. Fourth, I show that the exercise endurance of abl2 mutant mice is diminished, likely due to the compensatory reduction in size of the diaphragm central tendon. Finally, I provide evidence for signaling between muscle cells and tendon cells that induces tendon cell differentiation.
|Advisor:||Burden, Steven J.|
|Commitee:||Knaut, Holger, Ringstad, Niels, Treisman, Jessica|
|School:||New York University|
|Department:||Basic Medical Science|
|School Location:||United States -- New York|
|Source:||DAI-B 78/12(E), Dissertation Abstracts International|
|Subjects:||Biology, Genetics, Developmental biology|
|Keywords:||Muscle, Myoblast, Myogenesis, Proliferation, Tendon|
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