Regulation of vertebrate muscle differentiation by thyroid hormone: the role of the myoD gene family.
Skeletal myoblasts have their origin early in embryogenesis within specific somites. Determined myoblasts are committed to a myogenic fate; however, they only differentiate and express a muscle-specific phenotype after they have received the appropriate environmental signals. Once proliferating myoblasts enter the differentiation programme they withdraw from the cell cycle and form post-mitotic multinucleated myofibres (myogenesis); this transformation is accompanied by muscle-specific gene expression. Muscle development is associated with complex and diverse protein isoform transitions, generated by differential gene expression and mRNA splicing. The myofibres are in a state of dynamic adaptation in response to hormones, mechanical activity and motor innervation, which modulate differential gene expression and splicing during this functional acclimatisation. This review will focus on the profound effects of thyroid hormone on skeletal muscle, which produce alterations in gene and isoform expression, biochemical properties and morphological features that precipitate in modified contractile/mechanical characteristics. Insight into the molecular events that control these events was provided by the recent characterisation of the MyoD gene family, which encodes helix-loop-helix proteins; these activate muscle-specific transcription and serve as targets for a variety of physiological stimuli. The current hypothesis on hormonal regulation of myogenesis is that thyroid hormones (1) directly regulate the myoD and contractile protein gene families, and (2) induce thyroid hormone receptor-transcription factor interactions critical to gene expression.
Muscat
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GE
University of Queensland Centre for Molecular and Cellular Biology, St Lucia, Australia.
Downes
M
M
Dowhan
D H
DH
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000196:embryology* / Q000254:growth & development; D017570:MyoD Protein / Q000235:genetics* / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism* / Q000494:pharmacology; D014714:Vertebrates / Q000196:embryology
D017570:MyoD Protein; D013963:Thyroid Hormones