Ectopic Pax-3 Activates MyoD and Myf-5 Expression in Embryonic Mesoderm and Neural Tissue

Summary induce myogenic precursors or to maintain and expand a population of already specified cells (see Munsterberg To understand how the skeletal muscle lineage is in- and Lassar, 1995, and references therein). We have duced during vertebrate embryogenesis, we have shown that myogenesis of explanted presegmental sought to identify the regulatory molecules that medi- plate mesoderm (isolated from a stage 10 chick embryo) ate induction of the myogenic regulatory factors MyoD requires two signals from axial tissues, one emanating and Myf-5. In this work, we demonstrate that either from the floor plate-notochord complex and the other signals from the overlying ectoderm or Wnt and Sonic from more dorsal regions of the neural tube (Mun- hedgehog signals can induce somitic expression of sterberg and Lassar, 1995). Consistent with these find- the paired box transcription factors, Pax-3 and Pax-7, ings, Emerson and colleagues recently reported that concomitant with expression of Myf-5 and prior to that signals from the notochord are required to initiate quail of MyoD. Moreover, infection of embryonic tissues in MyoD expression and that signals from the neural tube vitro with a retrovirus encoding Pax-3 is sufficient to are required to maintain MyoD expression in ovo (Pow- induce expression of MyoD, Myf-5, and myogenin in nall et al., 1996). both paraxial and lateral plate mesoderm in the ab- The muscle-promoting signal from the floor plate- sence of inducing tissues as well as in the neural tube. notochord complex can be mimicked by the signaling Together, these findings imply that Pax-3 may mediate molecule Sonic hedgehog (Shh), and the muscle-pro- activation of MyoD and Myf-5 in response to muscle- moting signal from the neural tube can be mimicked by inducing signals from either the axial tissues or overly- cell lines programmed to express either Wnt-1 or Wnt-3 ing ectoderm and identify Pax-3 as a key regulator of (Munsterberg et al., 1995; Stern et al., 1995). Because somitic myogenesis.