Retinoic acid signalling regulates branchiomeric neck muscle development at the head/trunk interface

ABSTRACT Skeletal muscles of the head and trunk originate in distinct lineages with divergent regulatory programmes converging on activation of myogenic determination factors. Branchiomeric head and neck muscles share a common origin with cardiac progenitor cells in cardiopharyngeal mesoderm (CPM). The retinoic acid (RA) signalling pathway is required during a defined early time window for normal deployment of cells from posterior CPM to the heart. Here, we show that blocking RA signalling in the early mouse embryo also results in selective loss of the trapezius neck muscle, without affecting other skeletal muscles. RA signalling is required for robust expression of myogenic determination factors in posterior CPM and subsequent expansion of the trapezius primordium. Lineage-specific activation of a dominant-negative RA receptor reveals that trapezius development is not regulated by direct RA signalling to myogenic progenitor cells in CPM, or through neural crest cells, but indirectly through the somitic lineage, closely apposed with posterior CPM in the early embryo. These findings suggest that trapezius development is dependent on precise spatiotemporal interactions between cranial and somitic mesoderm at the head/trunk interface.