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 end identify Pax-3 as a key regulator of somitic myogenesis.
Bibliographical noteFunding Information:
Correspondence should be addressed to A. B. L. We would like to thank Hazel Sive, Charlie Ordahl, members of the Lassar laboratory, and our anonymous reviewers for their thoughtful and insightful comments on this work; Donna Fekete, Connie Cepko, and Cliff Tabin for help with avian retrovirology; Michael Levin for assistance with DiI injection into chick neural tube; Bruce M. Paterson and Sara Hitchcock-DeGregori for antibodies against MyoD and Troponin T/I, respectively; and Rudy Balling and Haruhiko Koseki for providing the chick Pax-1 sequence prior to publication. This work was supported by a grant to A. B. L. from the National Science Foundation and grants to M. G. from the National Institutes of Health, the March of Dimes, and the Pew Charitable Trusts. This work was done during the tenure of an established investigatorship to A. B. L. from the American Heart Association. M. M. was supported by fellowships from the Spanish Ministry of Education and Science/Fulbright and the Human Frontier Science Program Organization. A. E. M. was supported by a fellowship from the Muscular Dystrophy Association. R. R. was supported by a fellowship from the Fulbright Foundation.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology (all)