Keep Your Friends Close: Cell-Cell Contact and Skeletal Myogenesis

Development of skeletal muscle is a multistage process that includes lineage commitment of multipotent progenitor cells, differentiation and fusion of myoblasts into multinucleated myofibers, and maturation of myofibers into distinct types. Lineage- specific transcriptional regulation lies at the core of this process, but myogenesis is also regulated by extracellular cues. Some of these cues are initiated by direct cell-cell contact between muscle precursor cells themselves or between muscle precursors and cells of other lineages. Examples of the latter include interaction of migrating neural crest cells with multipotent muscle progenitor cells, muscle interstitial cells with myoblasts, and neurons with myofibers. Among the signaling factors involved are Notch ligands and receptors, cadherins, Ig superfamily members, and Ephrins and Eph receptors. In this article we describe recent progress in this area and highlight open questions raised by the findings.