Clonal analysis reveals common lineage relationships between head muscles and second heart field derivatives in the mouse embryo

Abstract

SUMMARYHead muscle progenitors in pharyngeal mesoderm are present in close proximity to cells of the second heart field and show overlapping patterns of gene expression. However, it is not clear whether a single progenitor cell gives rise to both heart and head muscles. We now show that this is the case, using a retrospective clonal analysis in which an nlaacZ sequence, converted to functional nlacZ after a rare intragenic recombination event, is targeted to the  c -actin gene, expressed in all developing skeletal and cardiac muscle. We distinguish two branchiomeric head muscle lineages, which segregate early, both of which also contribute to myocardium. The first gives rise to the temporalis and masseter muscles, which derive from the first branchial arch, and also to the extraocular muscles, thus demonstrating a contribution from paraxial as well as prechordal mesoderm to this anterior muscle group. Unexpectedly, this first lineage also contributes to myocardium of the right ventricle. The second lineage gives rise to muscles of facial expression, which derive from mesoderm of the second branchial arch. It also contributes to outflow tract myocardium at the base of the arteries. Further sublineages distinguish myocardium at the base of the aorta or pulmonary trunk, with a clonal relationship to right or left head muscles, respectively. We thus establish a lineage tree, which we correlate with genetic regulation, and demonstrate a clonal relationship linking groups of head muscles to different parts of the heart, reflecting the posterior movement of the arterial pole during pharyngeal morphogenesis. KEY WORDS: Retrospective clonal analysis, Head muscles, Second heart field, MouseClonal analysis reveals common lineage relationships between head muscles and second heart field derivatives in the mouse embryo

Clonal analysis reveals a common origin between nonsomite-derived neck muscles and heart myocardium

“…No clonal relationship was observed between the trapezius group of muscles and masticatory, or facial expression, head muscles ( Fig. 2A and Table 1), derived from the first and second branchial arches, respectively (14). Somitic neck muscles, marked by genetic tracing with Pax3 Cre , but not by the Mef2c-AHF-Cre transgene, and muscles in the trunk or limbs also showed no clonality with the trapezius group ( Fig.…”

“…1 C and D). The Mef2c (myocyte enhancer factor 2c) enhancer is activated in the anterior SHF (21), and when Mef2c-Cre transgenic mice are crossed with the Rosa26 R-nlacZ/+ reporter line, labeling is seen in head muscles, notably those derived from the first branchial arch (14), as well as in myocardium of the pulmonary trunk, aorta, and right ventricle. The trapezius and sternocleidomastoid muscles are also labeled using this Cre line, as shown for the trapezius muscles on whole-mount X-gal-stained embryos at embryonic day (E)14.5 and E12.5 ( Fig.…”

“…Schema showing the lineage relationship between nonsomitic neck muscles of the trapezius group and myocardium. The first two lineages (in blue) contribute to the nonsomitic head muscles, derived from the first (1st) and second (2nd) branchial arches (BA), and to arterial pole myocardium (14). A third lineage (in mauve) contributes to the trapezius muscle group as well as to venous pole myocardium, with an additional contribution to the pulmonary trunk, and a contribution to the splenius muscle (orange).…”

“…Cells with divergent cardiac and skeletal muscle fates in this cardiopharyngeal mesoderm are similarly labeled by genetic tracing (13). Furthermore, retrospective clonal analysis in the mouse embryo has shown that masticatory muscles of the head and right ventricular myocardium originate from common progenitor cells, whereas facial expression muscles share a common clonal origin with the arterial pole of the heart, such that myocardium at the base of the pulmonary trunk or the aorta is clonally related to left or right facial expression muscles, respectively (14). Cardiopharyngeal mesoderm cells that give rise to both cardiac and skeletal muscle derivatives are already present in urochordates, such as the ascidian Ciona intestinalis, where the equivalent of an SHF can be distinguished (15).…”

Morphogenesis of outflow tract rotation during cardiac development: The pulmonary push concept

“…It has been demonstrated previously that the myocardial part of the OFT, comprising both the subaortic and subpulmonary myocardium, is derived from the second heart field (Cai et al, 2003). This myocardium has been shown to have a common lineage relationship to the right-and left-sided head muscles, respectively (Lescroart et al, 2010).…”