Role of Akap12 in the Muscle Morphogenesis and Locomotion in Zebrafish : 제브라피쉬의 근육발달과 운동성에 관련된 Akap12 단백질의 기능 연구

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약학대학 약학과
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서울대학교 대학원
학위논문 (박사)-- 서울대학교 대학원 : 약학과, 2015. 2. 김규원.
Role of Akap12 in the Muscle Morphogenesis and Locomotion in Zebrafish

Hyun Ho Kim
Division of Pharmaceutical Bioscience
College of Pharmacy
The Graduate School
Seoul National University

Swimming behavior in fish is driven by coordinated contractions of muscle fibers. As in other vertebrates, zebrafish skeletal muscle cells can be classified as slow or fast fibers on the basis of their physiological functions. In zebrafish, slow muscle cell migration is crucial for the formation of the muscle network
slow myoblasts, which arise from medial adaxial cells, migrate radially to the lateral surface of the trunk and tail during embryogenesis. At the level of the horizontal myoseptum, adaxial cells at the medial surface do not migrate but rather remain associated with the notochord
these cells are termed muscle pioneers. Fast muscle cells are generated by the elongation and fusion of initially rounded lateral presomitic mesoderm cells after their slow muscle migration. These dramatic morphogenic changes during somitogenesis are critical for normal muscle contractility and function. Although the molecular mechanisms that specify myogenic fate have been extensively studied, relatively little is known about how the normal morphogenic movements of myoblasts lead to early locomotor behaviors. This study found that the zebrafish A-kinase anchoring protein (akap)12 isoforms akap12α and akap12β are required for muscle morphogenesis and locomotor activity. Embryos deficient in akap12 exhibited reduced spontaneous coiling, touch response, and free swimming. Akap12-depleted slow but not fast muscle cells were misaligned, suggesting that the behavioral abnormalities resulted from specific defects in slow muscle patterning
indeed, slow muscle cells and muscle pioneers in these embryos showed abnormal migration in a cell-autonomous manner. Taken together, these results suggest that akap12 plays a critical role in the development of zebrafish locomotion by regulating the normal morphogenesis of muscles.
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