Neural Crest Cells Contribute to Normal Aorticopulmonary Septation

Abstract

By analyzing the hearts of quail-chick chimeras, it was found that neural crest cells at the level of occipital somites 1 to 3 migrate to the region of the aorticopulmonary septum. Bilateral removal of this neural crest population prior to migration causes malformation of the aorticopulmonary septum resulting in common arterial outflow channels or transposition of the great vessels.

Controlled levels of canonical Wnt signaling are required for neural crest migration

“…They are induced along the entire length of neuraxis as a bilateral, segmented stripe of cells at the lateral border of the neural plate and nonneural ectoderm (Hall, 2008;Le Douarin and Kalcheim, 1999;Sauka-Spengler and Bronner-Fraser, 2008;Steventon et al, 2005). NC cells are subdivided into cranial (Graham et al, 2004;Cordero et al, 2011), cardiac (Kirby et al, 1983;Keyte and Hutson, 2012), vagal (Kuo and Erickson, 2011;Peters-Van Der Sanden et al, 1993;Burns and Le Douarin, 1998;Yntema and Hammond, 1954), trunk (Bronner-Fraser and Fraser, 1989;Serbedzija et al, 1994) and sacral (Burns and Le Douarin, 1998;Anderson et al, 2006) NC cells due to their diversity along neuraxis ( Fig.1.1A). Upon closure of the neural plate, NC cells undergo epithelial-to-mesenchymal transition (EMT) (Ahlstrom and Erickson, 2009;Alfandari et al, 2010;Berndt et al, 2008 andDuband, 2010) allowing them to delaminate from prospective neural tube and migrate throughout the embryo ( Fig.1.1B).…”

“…Only a small amount of cranial NC cells invade the underlying mesoderm (Noden, 1975(Noden, , 1988 (Kuo and Erickson, 2011). Those NC cells contain a subset of the cardiac NC, which mainly contributes to the connective tissue and smooth muscles (Kirby et al, 1983;Kirby and Waldo, 1995 Helbling et al,1998), while their ligand, namely ephrin-B2 is expressed in migrating NC cells/mesoderm of the adjacent second arch Smith et al, 1997). Using truncated forms of those proteins it has been shown that their interactions provide a repulsive signaling allowing the proper segregation of the second and third-arch NC cells and additionally target third-arch NC cells to their proper destination .…”

MAP3Ks as central regulators of cell fate during development

“…The outflow tract tissue is partially derived from neural crest. The migration of the cardiac neural crest is essential for parasympathetic innervation of the heart as well as completion of aortic-pulmonary septation (Kirby et al, 1983). Additionally, the JNK pathway has been implicated downstream of WNT signaling (Yamanaka et al, 2002), and WNT factors are critical to outflow tract formation.…”

Endothelial Notch1 Is Required for Proper Development of the Semilunar Valves and Cardiac Outflow Tract

“…In addition, a subpopulation of endothelial cells that line the OFT undergo endothelial‐to‐mesenchymal transition to form the OFT cushions. These mesenchymal cells are joined by the migrating cardiac neural crest cells, which are required for septation of the aorta and pulmonary artery 9, 10, 11. Proper migration and signaling of all 3 cell lineages, the SHF, cardiac neural crest and endothelial‐derived mesenchymal cells are required for normal OFT cushion development and semilunar valve remodeling.…”