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.