期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：5
页码：1446-1451
DOI：10.1073/pnas.1424538112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceHead muscles, derived from the first and second pharyngeal arches, share common progenitors with myocardial cells of the heart. This is in contrast to somite-derived skeletal muscles of the trunk and limbs. Neck muscles, located in the transition zone between head and trunk, have both a somitic and nonsomitic origin. We now demonstrate a clonal relationship between nonsomitic neck muscles and myocardial cells located in the atria, inflow and outflow regions of the heart. This is distinct from that of the two head muscle lineages. Formation of these neck muscles, like those in the head, depends on a gene regulatory network shared with myocardial progenitors. We thus identify a third clonal group within cardiopharyngeal mesoderm, with implications for human malformations. Neck muscles constitute a transition zone between somite-derived skeletal muscles of the trunk and limbs, and muscles of the head, which derive from cranial mesoderm. The trapezius and sternocleidomastoid neck muscles are formed from progenitor cells that have expressed markers of cranial pharyngeal mesoderm, whereas other muscles in the neck arise from Pax3-expressing cells in the somites. Mef2c-AHF-Cre genetic tracing experiments and Tbx1 mutant analysis show that nonsomitic neck muscles share a gene regulatory network with cardiac progenitor cells in pharyngeal mesoderm of the second heart field (SHF) and branchial arch-derived head muscles. Retrospective clonal analysis shows that this group of neck muscles includes laryngeal muscles and a component of the splenius muscle, of mixed somitic and nonsomitic origin. We demonstrate that the trapezius muscle group is clonally related to myocardium at the venous pole of the heart, which derives from the posterior SHF. The left clonal sublineage includes myocardium of the pulmonary trunk at the arterial pole of the heart. Although muscles derived from the first and second branchial arches also share a clonal relationship with different SHF-derived parts of the heart, neck muscles are clonally distinct from these muscles and define a third clonal population of common skeletal and cardiac muscle progenitor cells within cardiopharyngeal mesoderm. By linking neck muscle and heart development, our findings highlight the importance of cardiopharyngeal mesoderm in the evolution of the vertebrate heart and neck and in the pathophysiology of human congenital disease.
