| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1992: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1991: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
The recent identification of MyoD and related proteins, myogenin, MRF4/herculin/Myf-6, and Myf-5 has opened up new approaches to investigate molecular basis of muscle development. Non-muscle cells, such as embryonic fibroblasts, are converted to muscle cells after the expression of these myogenic proteins.
These factors belong to a family of regulatory proteins, designated as basic-helix-loop-helix proteins, which bind in vitro to the consensus sequence referred to as an E-box.
How individual members of these factors are involved in muscle development has not been clarified yet.
Studies on regulation of the myogenin gene in vitro and in vivo suggest that the role of the myogenin gene is crucial for muscle formation. It is expressed or activated in all the established myoblast cell lines so far examined. During embryogenesis, myogenin gene transcripts are initially detected in somites and in limb buds. Although expression of the myogenin gene dramatically decreases after birth, denervation
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reactivates its transcription. These studies suggest the involvement of myogenin not only in muscle cell terminal differentiation but also in the preceding myogenic processes. Thus, studies on regulatory mechanisms of the myogenin gene should illuminate molecular basis of myogenesis.
In an attempt to understand regulatory mechanisms which govern transcriptional activation of the myogenin gene, transgenic mice bearing the lacZ gene driven by the upstream region of the myogenin gene were generated. Stereoscopic visualization of LacZ-positive cells of these transtenic mouse embryos revealed that the upstream region of the myogenin gene conferred its transcriptional activation in cells of the skeletal muscle-lineages in somites, limb buds, and visceral arches. Moreover, transient LacZ expression in newly formed somites in addition to its strong activation in myotomal regions of mature somites with a rostro-caudal gradient raised the possibility that myogenin is transcriptionally activated in immature somites before myotome formation. Less
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