Muscles of the trunk originate from the segmented somites, whereas head muscles arise independently from the cardiopharyngeal mesoderm (CPM) located anterior to the somites ( Diogo et al., 2015 Sambasivan et al., 2011). Considerable diversity in developmental origins and regulation of skeletal muscles point to important functional differences that remain unexplored. Our findings establish a Tbx1-Isl1-Met genetic hierarchy that uniquely regulates esophagus myogenesis and identify distinct genetic signatures that can be used as framework to interpret pathologies arising within CPM derivatives.Įvolution of vertebrates has been marked by the emergence of muscularized jaws that transitioned them from filter feeders to active predators ( Glenn Northcutt, 2005). These observations highlight the functional relevance of a smooth and striated muscle progenitor dialogue for ESM patterning. Further, genetic loss-of-function and pharmacological studies point to MET/HGF signaling for antero-posterior migration of esophagus muscle progenitors, where Hgf ligand is expressed in adjacent smooth muscle cells. Using mouse chimeras, we show that the transcription factors Tbx1 and Isl1 are required cell-autonomously for myogenic specification of ESM progenitors. Masticatory and esophagus striated muscles (ESM) share a common cardiopharyngeal mesoderm (CPM) origin, however ESM are unusual among striated muscles as they are established in the absence of a primary skeletal muscle scaffold. In most vertebrates, the upper digestive tract is composed of muscularized jaws linked to the esophagus that permits food ingestion and swallowing.

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