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 verteb rate embryogenesis, we have sought to identify the regulatory molecule s that mediate induction of the myogenic regulatory factors MyoD and M yf-5. In this work, we demonstrate that either signals from the overly ing ectoderm or Wnt and Sonic hedgehog signals can induce semitic expr ession of the paired box transcription factors, Pax-3 and Pax-7, conco mitant with expression of Myf-5 and prior to that of MyoD. Moreover, i nfection of embryonic tissues in vitro with a retrovirus encoding Pax- 3 is sufficient to induce expression of MyoD, Myf-5, and myogenin in b oth paraxial and lateral plate mesoderm in the absence of inducing tis sues as well as in the neural tube. Together, these findings imply tha t 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 semitic myogenesis.