Fate of the mammalian cardiac neural crest

Abstract

A subpopulation of neural crest termed the cardiac neural crest is required in avian embryos to initiate reorganization of the outflow tract of the developing cardiovascular system. In mammalian embryos, it has not been previously experimentally possible to study the long-term fate of this population, although there is strong inference that a similar population exists and is perturbed in a number of genetic and teratogenic contexts. We have employed a two-component genetic system based on Cre/lox recombination to label indelibly the entire mouse neural crest population at the time of its formation, and to detect it at any time thereafter. Labeled cells are detected throughout gestation and in postnatal stages in major tissues that are known or predicted to be derived from neural crest. Labeling is highly specific and highly efficient. In the region of the heart, neural-crest-derived cells surround the pharyngeal arch arteries from the time of their formation and undergo an altered distribution coincident with the reorganization of these vessels. Labeled cells populate the aorticopulmonary septum and conotruncal cushions prior to and during overt septation of the outflow tract, and surround the thymus and thyroid as these organs form. Neural-crest-derived mesenchymal cells are abundantly distributed in midgestation (E9.5-12.5), and adult derivatives of the third, fourth and sixth pharyngeal arch arteries retain a substantial contribution of labeled cells. However, the population of neural-crest-derived cells that infiltrates the conotruncus and which surrounds the noncardiac pharyngeal organs is either overgrown or selectively eliminated as development proceeds, resulting for these tissues in a modest to marginal contribution in late fetal and postnatal life.

The Cardiac Neural Crest Cells in Heart Development and Congenital Heart Defects

“…In addition to ablation models, lineage tracing, which identifies and tracks cell populations in vivo, provides an advanced way to uncover NC-derived cardiovascular contributions. Ablation and lineage tracing experiments have shown that cardiac NCCs in amniotes originate between the optic vessel and third somite, and migrate to pharyngeal arches three, four and six, to contribute to smooth muscle development, septation of the OFT, and patterning of the septa, valves, and aortic arch arteries [7,40,41]. Recently, Tang and colleagues, using retroviral labeling in chicks and Wnt1-Cre reporter lines in mice, found that a portion of NCCs also contributes to ventricle trabecular myocardium, however, further and more in-depth lineage mapping of cardiac NCCs is needed to confirm these conclusions [42].…”

Excess Provisional Extracellular Matrix: A Common Factor in Bicuspid Aortic Valve Formation

“…Mesenchymal cells of neural crest origin (cardiac neural crest, CNC) migrate from the hindbrain into the distal OFT and populate the endocardial cushions beginning at approximately E9.5. As OFT remodeling progresses, CNC cells proliferate, condense, and migrate proximally toward the right ventricle [18][19][20]. OFT cushions in the proximal region are also composed of mesenchymal cells that arise from an endocardial to mesenchymal transformation (EndoMT).…”

“…By approximately E11.5, the major OFT cushions join and fuse at the midline; this fusion separates the common OFT into the separate pulmonary and aortic channels (P and A in Figure 1A,B,B',C'). As the AoV and PV are formed and sculpted throughout OFT remodeling, a subset of myocardial cells [26], as well as a portion of CNC cells, differentiate into smooth muscle cells (SMCs) and contribute to the aortic root and ascending aortic wall, respectively [20,27]. However, in spite of the developmental interdependence of the aortic valve and ascending aorta, few genes have been discovered that, when disrupted, give rise to both BAV and ascending aortopathies [28].…”

Deregulated Rac1 Activity in Neural Crest Controls Cell Proliferation, Migration and Differentiation During Midbrain Development

“…Originated as ectodermal cells at the border of the neural plate at the dorsal neural tube, NCCs undergo epithelial to mesenchymal transition (EMT), then migrate to the ventral destinations. Lineage tracing studies demonstrate that NCCs give rise to a broad range of cell types in craniofacial and cardiovascular tissues (Chai et al, 2000;Jiang et al, 2000Jiang et al, , 2002Yoshida et al, 2008). NCCs derivatives are also identified in the developing midbrain (Jiang et al, 2002;Lewis et al, 2013).…”