Evolutionary and developmental origins of the cardiac neural crest: building a divided outflow tract

Abstract

The cardiac neural crest cells (CNCCs) have played an important role in the evolution and development of the vertebrate cardiovascular system: from reinforcement of the developing aortic arch arteries early in vertebrate evolution, to later orchestration of aortic arch artery remodeling into the great arteries of the heart, and finally outflow tract septation in amniotes. A critical element necessary for the evolutionary advent of outflow tract septation was the co-evolution of the cardiac neural crest cells with the second heart field. This review highlights the major transitions in vertebrate circulatory evolution, explores the evolutionary developmental origins of the CNCCs from the third stream cranial neural crest, and explores candidate signaling pathways in CNCC and outflow tract evolution drawn from our knowledge of DiGeorge Syndrome.

Keywords: cardiac neural crest; evolution; outflow tract septation; pharyngeal arch artery remodeling; second heart field.

FIGURE 1

Circulation of oxygenated and de-oxygenated blood. (A) In most fish the circulation of blood creates a single loop. (B, C) In amphibians and reptiles, two loops form with the addition of the pulmonary circulation. However, the separation of oxygenated and de-oxygenated blood is more complete in reptiles than in amphibians. (D) Birds and mammals possess two separate circuits of oxygenated and de-oxygenated blood. A, atrium; V, ventricle; RA, LA, right and left atrium; RV, LV, right and left ventricle.

FIGURE 2

Cranial neural crest streams in relation to the developing cardiac vasculature of divided (A) and un-divided (B) outflow tracts. (A) In mammals and birds, the cells arising from the third cranial neural crest stream (shown in green) contribute to the aortic arch arteries and eventually the outflow tract (dashed green arrow). (B) In teleosts, cells from the third cranial neural crest stream contribute to the branchial arches that will bear gills arch arteries.

FIGURE 3

The evolution of aortic arches and cardiac chambers in vertebrates. (A) Primitive fishes, represented by sharks, have six paired gill arches. (B) In teleosts, the gill arch arteries are reduced to form four pairs in the caudal branchial arches. (C) Lungfish have both gills and a pulmonary circulation with the gill arches corresponding to arches two, five, and six. During air respiration, the blood is shunted through arches three and four, while the ductus arteriosus in arch six shunts oxygen-poor blood away from the gills and to the lungs. (D) In adult amphibians, the gill arches are lost and the aortic arch vasculature remains bilaterally symmetrical. Oxygenated and de-oxygenated blood enter the ventricle through the right and left atrium and leaves the heart through a single outflow tract containing a spiral valve. (E) In mammals, the fourth aortic arch arteries become bilaterally asymmetrical and the outflow tract separates into two distinct outflow vessels. (F) Birds also have a completely divided outflow tract with asymmetrical aortic arch arteries. (G) In reptiles such as the turtle, aortic arch artery four remains bilateral but is divided at the base of the outflow tract. The outflow tract is divided into three arteries: right and left aortic arch arteries and the pulmonary artery. In all figures cranial is to the top and caudal is to the bottom.

FIGURE 4

Comparative anatomy of vertebrate hearts. (A) Teleosts have a single atrium and ventricle with an outflow consisting of the bulbus arteriosus. Only deoxygenated blood pumps through the teleost heart. (B) Frogs have two atria and one ventricle in which oxygenated and de-oxygenated blood can mix. The blood exits the ventricle through a single outflow vessel containing a spiral septum. (C) Turtles have two atria and a ventricle that is partitioned into three sections. The dorsal left atrial space directs blood to the right aorta while the ventral left ventricle directs blood to the left aorta. The right side of the ventricle directs blood to the pulmonary artery. (D, E) In the avian and mammalian hearts, the ventricle is completely divided with a single aorta and a pulmonary artery.