COMBINATORIAL SIGNALING BY SONIC HEDGEHOG AND WNT FAMILY MEMBERS INDUCES MYOGENIC BHLH GENE-EXPRESSION IN THE SOMITE

We have demonstrated previously that a combination of signals from the neural tube and the floor plate/notochord complex synergistically ind uce the expression of myogenic bHLH genes and myogenic differentiation markers in unspecified somites. In this study we demonstrate that Son ic hedgehog (Shh), which is expressed in the floor plate/notochord, an d a subset of Wnt family members (Wnt-1, Wnt-3, and Wnt-4), which are expressed in dorsal regions of the neural tube, mimic the muscle induc ing activity of these tissues. In combination, Shh and either Wnt-1 or Wnt-3 are sufficient to induce myogenesis in semitic tissue in vitro. Therefore, we propose that myotome formation in vivo may be directed by the combinatorial activity of Shh secreted by ventral midline tissu es (floor plate and notochord) and Wnt ligands secreted by the dorsal neural tube.