The inhibition of differentiation caused by TGFβ in fetal myoblasts is dependent upon selective expression of PKCθ: A possible molecular basis for myoblast diversification during limb histogenesis

Abstract

Embryonic and fetal skeletal myoblasts are responsible for the formation of primary and secondary fibers in mammals, but the mechanism which diversifies their fate is unknown. In vitro, embryonic myoblasts are resistant to the differentiation inhibitory effects of transforming growth factor β and phorbol esters. Thus, differential expression of specific molecules involved in the transduction of extracellular signals may contribute to the different phenotypes. We report here that protein kinase C θ, but none of the other known protein kinase C isoforms, is selectively expressed in fetal and postnatal muscle cells (at both the myoblast and myotube stage) in vitro and in vivo. By contrast, embryonic myoblasts and myotubes do not express protein kinase C θ in vitro or in vivo. This difference is causally related to a differential response to transforming growth factor β, since overexpression of protein kinase C θ, but not of protein kinase C α or ζ, in embryonic myoblasts makes these cells sensitive to transforming growth factor β. These data demonstrate for the first time that a protein kinase C isoform is a key component of the signal transduction cascade which follows exposure of myoblasts to transforming growth factor β. They also suggest a specific role for protein kinase C θ in determining the fate of different myoblasts during muscle histogenesis.