Endothelium in the pharyngeal arches 3, 4 and 6 is derived from the second heart field

Abstract

Oxygenated blood from the heart is directed into the systemic circulation through the aortic arch arteries (AAAs). The AAAs arise by remodeling of three symmetrical pairs of pharyngeal arch arteries (PAAs), which connect the heart with the paired dorsal aortae at mid-gestation. Aberrant PAA formation results in defects frequently observed in patients with lethal congenital heart disease. How the PAAs form in mammals is not understood. The work presented in this manuscript shows that the second heart field (SHF) is the major source of progenitors giving rise to the endothelium of the pharyngeal arches 3 – 6, while the endothelium in the pharyngeal arches 1 and 2 is derived from a different source. During the formation of the PAAs 3 – 6, endothelial progenitors in the SHF extend cellular processes toward the pharyngeal endoderm, migrate from the SHF and assemble into a uniform vascular plexus. This plexus then undergoes remodeling, whereby plexus endothelial cells coalesce into a large PAA in each pharyngeal arch. Taken together, our studies establish a platform for investigating cellular and molecular mechanisms regulating PAA formation and alteration that lead to disease.

Reduced maternal vitamin A status increases the incidence of normal aortic arch variants

“…During early stages of heart development vitamin A is absorbed through the visceral endoderm of the yolk sac and then across the placenta beginning mid-gestation (Comptour et al, 2016;Zohn & Sarkar, 2010). Retinoic acid signaling is required for multiple aspects of heart development including formation and remodeling of the aortic arch through a requirement in patterning of the SHF and then formation of the PAAs (Verzi et al, 2005;Wang et al, 2017).…”

“…Abnormalities in the formation of the fourth PAA identified in our study are consistent with known consequences of reductions in retinoic acid signaling on PAA development. In addition to migration to the outflow tract, SHF cells migrate to the developing pharyngeal mesenchyme where they organize into an endothelial plexus that coalesces to form the endothelium of the PAAs, a process also influenced by retinoic acid signaling (Li et al, 2012;Wang et al, 2017). In addition to migration to the outflow tract, SHF cells migrate to the developing pharyngeal mesenchyme where they organize into an endothelial plexus that coalesces to form the endothelium of the PAAs, a process also influenced by retinoic acid signaling (Li et al, 2012;Wang et al, 2017).…”

“…Once initial induction and patterning of the SHF is complete, aberrant reduction in retinoic acid signaling can result in premature differentiation and consequently reduced contribution of the SHF to the outflow tract (Li et al, 2012). In addition to migration to the outflow tract, SHF cells migrate to the developing pharyngeal mesenchyme where they organize into an endothelial plexus that coalesces to form the endothelium of the PAAs, a process also influenced by retinoic acid signaling (Li et al, 2012;Wang et al, 2017). Multiple other cell types also participate in formation of the PAAs and development of these is also influenced by retinoic acid signaling.…”

“…SHF cells migrate to the developing pharyngeal mesenchyme where they organize into an endothelial plexus that coalesces to form the endothelium of the third through sixth PAAs (Li, Pashmforoush, & Sucov, 2012;Verzi, McCulley, De Val, Dodou, & Black, 2005;Wang et al, 2017). Neural crest cells migrate from the dorsal neural tube to the pharyngeal arches and contribute to the smooth muscle of the of the third, fourth, and sixth PAAs as well as the pharyngeal mesenchyme where they differentiate into a variety of cell types including cartilage, bone and connective tissue (Keyte & Hutson, 2012).…”

Cardiac competence of the paraxial head mesoderm fades concomitant with a shift towards the head skeletal muscle programme

“…The vertebrate head mesoderm is the first embryonic mesoderm type to emerge during gastrulation (Camp et al, 2012;Garcia-Martinez and Schoenwolf, 1993). It delivers the heart (reviewed in (Meilhac and Buckingham, 2018;Spater et al, 2014), the great vessels (Paffett-Lugassy et al, 2013;Wang et al, 2017), the smooth muscle collar of the cardiac outflow (Waldo et al, 2005), genuine craniofacial and oesophageal skeletal muscles (reviewed in (Schubert et al, 2018) and parts of the skull base ((Jandzik et al, 2015); reviewed in (Kuratani, 2005)). The head mesoderm has received quite some attention since in a subpopulation of cardiogenic cells, the secondary heart field (SHF) cells, differentiation is delayed.…”