Epiblast cells that express MyoD recruit pluripotent cells to the skeletal muscle lineage

Embryonic stem cells are derived from the epiblast. A subpopulation of epiblast cells expresses MyoD mRNA and the G8 antigen in vivo. G8 positive (G8(pos)) and G8 negative (G8(neg)) populations were isolated by magnetic cell sorting. Nearly all G8(pos) cells switched from E- to N-cadherin and differentiated into skeletal muscle in culture. G8(neg) cells were impaired in their ability to switch cadherins and few formed skeletal muscle. Medium conditioned by G8(pos) cells stimulated skeletal myogenesis and N-cadherin synthesis in G8(neg) cultures. The effect of conditioned medium from G8(pos) cultures was inhibited by bone morphogenetic protein (BMP) 4. Treatment of G8(neg) cells with a soluble form of the BMP receptor-IA or Noggin promoted N-cadherin synthesis and skeletal myogenesis. These results demonstrate that MyoD-positive epiblast cells recruit pluripotent cells to the skeletal muscle lineage. The mechanism of recruitment involves blocking the BMP signaling pathway.