Ectopic Pax-3 activates MyoD and Myf-5 expression in embryonic mesoderm and neural tissue.

To understand how the skeletal muscle lineage is induced during vertebrate embryogenesis, we have sought to identify the regulatory molecules that mediate induction of the myogenic regulatory factors MyoD and Myf-5. In this work, we demonstrate that either signals from the overlying ectoderm or Wnt and Sonic hedgehog signals can induce somitic expression of the paired box transcription factors, Pax-3 and Pax-7, concomitant with expression of Myf-5 and prior to that of MyoD. Moreover, infection of embryonic tissues in vitro with a retrovirus encoding Pax-3 is sufficient to induce expression of MyoD, Myf-5, and myogenin in both paraxial and lateral plate mesoderm in the absence of inducing tissues as well as in the neural tube. Together, these findings imply that Pax-3 may mediate activation of MyoD and Myf-5 in response to muscle-inducing signals from either the axial tissues or overlying ectoderm and identify Pax-3 as a key regulator of somitic myogenesis.