Molecular-genetic mechanisms for the functionally determined isogene selections in muscle

Abstract

In embryonic development, differentiation consists in the modification of a fraction of the genes into a form irreversibly blocked from expression. In fetal development, there are further differentiation phenomena, often representing the selective expression of isogenes or members of a gene family. These subdifferentiations are reversibly determined by functional influences exerted by the nervous system and by hormones. The myosin heavy-chain (MHC) isogene family is a favorable case for such studies. In skeletal muscle, the MHC type is regulated by the innervation determining the myonal types slow (S) and fast (F). In the heart, the isoforms MHC α and β are regulated by thyroid hormone (TH). The details depend on the species. While TH always promotes α, the euthyroid state can be either α or β, the latter being the rule. In skeletal S and F types, the reversibility of regulation is demonstrated by the nerve-crossing experiment, which causes a reciprocal SF and FS reprogramming; this requires months, even years to be completed. Such reprogrammings are pleiotropic, affecting a number of type characteristics, which eventually reach a new functional harmony. Ongoing work is described on the question of whether the nerve communicates its influence by impulse patterns or by determinant substances.