MyoD − epiblast cells form skeletal muscle (red) if the BMP pathway is blocked.
The group has isolated a pool of cells from the embryonic epiblast that seems to be committed even before gastrulation to form skeletal muscle. These cells express mRNA for the MyoD transcription factor and form skeletal muscle in vitro if dissociated from other epiblast cells. Muscle formation in vitro requires a switch in expression from E- to N-cadherin, which also occurs as epiblast cells undergo gastrulation in vivo.
If separated from the muscle precursors, cells lacking MyoD retained E-cadherin and did not make muscle. However, when the MyoD− cells were treated with medium from the muscle precursors, they expressed N-cadherin and formed skeletal muscle. BMP-4 was able to block this inductive effect, and inhibition of the BMP receptor in MyoD− cells stimulated muscle formation. This suggests that the muscle precursors secrete a BMP antagonist, possibly Noggin, which recruits more cells to the muscle lineage.
The authors do not yet know whether this recruitment occurs via this mechanism in vivo but plan to test that question soon. They are hopeful that their results may be applied to stem cell–based treatments of degenerative muscle diseases. Injecting pluripotent cells with those that are already programmed to form muscle may produce more muscle than either cell type alone. ▪
