REGULATION OF VERTEBRATE MUSCLE DIFFERENTIATION BY THYROID-HORMONE - THE ROLE OF THE MYOD GENE FAMILY

Skeletal myoblasts have their origin early in embryogenesis within spe cific somites. Determined myoblasts are committed to a myogenic fate; however, they only differentiate and express a muscle-specific phenoty pe after they have received the appropriate environmental signals. Onc e proliferating myoblasts enter the differentiation programme they wit hdraw from the cell cycle and form post-mitotic multinucleated myofibr es (myogenesis); this transformation is accompanied by muscle-specific gene expression. Muscle development is associated with complex and di verse protein isoform transitions, generated by differential gene expr ession and mRNA splicing. The myofibres are in a state of dynamic adap tation in response to hormones, mechanical activity and motor innervat ion, which modulate differential gene expression and splicing during t his functional acclimatisation. This review will focus on the profound effects of thyroid hormone on skeletal muscle, which produce alterati ons in gene and isoform expression, biochemical properties and morphol ogical features that precipitate in modified contractile/mechanical ch aracteristics. Insight into the molecular events that control these ev ents was provided by the recent characterisation of the MyoD gene fami ly, which encodes helix-loop-helix proteins; these activate muscle-spe cific transcription and serve as targets for a variety of physiologica l stimuli. The current hypothesis on hormonal regulation of myogenesis is that thyroid hormones (1) directly regulate the myoD and contracti le protein gene families, and (2) induce thyroid hormone receptor-tran scription factor interactions critical to gene expression.