Localisation of transforming growth factor beta 1 in developing muscles: implications for connective tissue and fiber type pattern formation.

Skeletal muscles are highly ordered mixtures of cell types, with each muscle having its own characteristic pattern of fiber types, connective tissues, and vasculature. The precursors of the myogenic and connective elements of a muscle are initially intermixed and are proliferating and differentiating together in a manner that generates an ordered array of mature cells. The molecular basis of myogenesis is unknown, although in vitro studies have revealed numerous putative regulators. The results obtained from in vitro studies are not easily related to in vivo myogenesis because of a lack of information about the localisation of the putative regulators in developing muscles. The objective of this paper was therefore to describe the spatial and temporal distribution of transforming growth factor beta 1 (TGF-beta 1), a small peptide that affects cultured fibroblasts, myoblasts, and vascular endothelial cells. TGF-beta 1-immunoreactivity was associated with the epimysia, perimysia, and vasculature of the developing muscles. The expression of TGF-beta 1 within developing muscles had a distinct spatial and temporal pattern that correlated with the fate of adjacent myotubes. Myotubes which formed prior to the expression of TGF-beta 1 developed into slow fibers whereas those which formed adjacent to TGF-beta 1-containing connective tissue matured into fast fibers. The possibility that TGF-beta 1 is involved in the generation of the pattern of epi- and perimysia and/or fiber types is discussed.