Evolution and Development of Ventricular Septation in the Amniote Heart

Abstract

During cardiogenesis the epicardium, covering the surface of the myocardial tube, has been ascribed several functions essential for normal heart development of vertebrates from lampreys to mammals. We investigated a novel function of the epicardium in ventricular development in species with partial and complete septation. These species include reptiles, birds and mammals. Adult turtles, lizards and snakes have a complex ventricle with three cava, partially separated by the horizontal and vertical septa. The crocodilians, birds and mammals with origins some 100 million years apart, however, have a left and right ventricle that are completely separated, being a clear example of convergent evolution. In specific embryonic stages these species show similarities in development, prompting us to investigate the mechanisms underlying epicardial involvement. The primitive ventricle of early embryos becomes septated by folding and fusion of the anterior ventricular wall, trapping epicardium in its core. This folding septum develops as the horizontal septum in reptiles and the anterior part of the interventricular septum in the other taxa. The mechanism of folding is confirmed using DiI tattoos of the ventricular surface. Trapping of epicardium-derived cells is studied by transplanting embryonic quail pro-epicardial organ into chicken hosts. The effect of decreased epicardium involvement is studied in knock-out mice, and pro-epicardium ablated chicken, resulting in diminished and even absent septum formation. Proper folding followed by diminished ventricular fusion may explain the deep interventricular cleft observed in elephantsThe vertical septum, although indistinct in most reptiles except in crocodilians and pythonidsis apparently homologous to the inlet septum. Eventually the various septal components merge to form the completely septated heart. In our attempt to discover homologies between the various septum components we aim to elucidate the evolution and development of this part of the vertebrate heart as well as understand the etiology of septal defects in human congenital heart malformations.

A phenology of the evolution of endothermy in birds and mammals

“…Both the mammalian and avian four-chambered heart evolved from a three-chambered stem-amniote heart through ventricular septation (Poelmann et al, 2014). This crucial innovation evolved independently in the two endotherm lineages and is a good example of convergent evolution and the emergence of a common, concurrent innovation during the evolution of endothermy (Poelmann et al, 2014).…”

“…Both the mammalian and avian four-chambered heart evolved from a three-chambered stem-amniote heart through ventricular septation (Poelmann et al, 2014). This crucial innovation evolved independently in the two endotherm lineages and is a good example of convergent evolution and the emergence of a common, concurrent innovation during the evolution of endothermy (Poelmann et al, 2014). The new fourth heart chamber, the left ventricle, allowed the systemic blood pressure -the blood pressure between the heart and the body -to be separated from that of the pulmonary blood pressure -the blood pressure between the heart and the lungs -by eliminating the mixing of oxygenated and deoxygenated blood.…”

The Epicardium in Ventricular Septation During Evolution and Development

“…Our new model for separating the ventricles implicates more than one component and has consequences for understanding the development of central muscular ventricular septal defects. (Note: The development of the membranous and the outflow tract septum has not been specifically addressed in this study) Interestingly, elephants and some relatives including seacows show a very deep anterior interventricular sulcus [10]. The anatomy of the right ventricular septal band and the attachment of the tricuspid chordae tendineae suggest a diminished folding mechanism resulting in retention of an early embryonic state, also known as neoteny.…”

“…Furthermore, an epicardial sheet, characteristic for the folding septum, was not encountered. As a consequence, expansion of the ventricles results in anterior folding of the ventricular wall, but not of the posterior wall, probably because of the physical constraints imposed by attachment of the heart to the dorsal body wall [10].…”

“…Tbx5 expression showed gradients along the cardiac tube and so may be a useful marker for regionalisation of the heart [9]. For experimental details and full material and method description, we refer to [10].…”