Activin A inhibits formation of skeletal muscle during chick development.

In this study we investigated the effect of recombinant activin A on the differentiation of limb muscle precursors of chick embryos. We show that treatment with activin resulted in a downregulation of Pax-3 and MyoD expression within 6 h after treatment, whereas expression of Myf-5 and Pax-7 was largely unaffected. The effect on gene expression was transient because 1 day after activin exposure the development of the premuscle masses had proceeded, and Pax-3 and MyoD expression was reexpressed at normal levels. Unlike other transforming growth factors-beta, activin did not induce programmed cell death in limb mesenchyme, thus myogenic cells were not permanently lost. In high-density cultures of embryonic chick limb mesenchyme (micromass cultures), activin repressed the generation of Pax-7-expressing muscle precursors. Furthermore, in the presence of activin, fewer muscle precursors differentiated, and the population of differentiating cells failed to fuse and form myotubes. Our data suggest that activin reversibly inhibited expression of two transcription factors, Pax-3 and MyoD, and thus transiently inhibited proliferation and differentiation of limb muscle precursors. However, myogenic cells were not lost as they continued to express Pax-7 and Myf-5, and this may have allowed precursors to commence development after the activin effect faded. We suggest that activin acts in conjunction with a closely related signalling molecule, myostatin, to prevent excessive growth of skeletal muscle.