Distribution of the angles of the inflow and outflow tract planes.

<p>Depicted on the y axis are the number of specimen in each group, depicted on the x axis are the AV/VA angles, ranging from 0° to 90°, divided in 10 groups. AV: atrioventricular; VA: ventriculoarterial.</p

Anatomical relationships of the right and left ventricle and the aorta andpulmonary trunk.

<p>Anatomical relationships of the right and left ventricle and the aorta andpulmonary trunk.</p

Parallel stand of the inflow and outflow tract planes (0°-10°).

<p>In this case, each of the outflow tracts is closer to one inflow tract, which leads to streaming and keeps the blood flows separated. The depicted heart has a discordant ventriculoarterial connection, meaning the pulmonary trunk is connected to the morphologically left ventricle and the aorta is connected to the morphologically right ventricle and communicates with the morphologically left ventricle via the ventricular septal defect. The angle in this specific heart was 5°.Ao: Aorta; AV: atrioventricular valve; PT: pulmonary trunk; VSD: ventricular septal defect; Ao = Aorta. Blue: deoxygenated blood, red: oxygenated blood.</p

20°-70° angle of the inflow and outflow tract planes.

<p>One of the two outflow tracts is in closer proximity to both inflow tracts so that blood from both inflow tracts will enter this outflow tract, whereas the other outflow tract is only supplied by the one inflow tract it is closest to. The depicted heart has a discordant ventriculoarterial connection, meaning the pulmonary trunk is connected to the morphologically left ventricle and the aorta is connected to the morphologically right ventricle and communicates with the morphologically left ventricle via the ventricular septal defect. The angle in this specific heart was 45°.Ao: Aorta; AV: atrioventricular valve; PT: pulmonary trunk; VSD: ventricular septal defect; Ao = Aorta. Blue: deoxygenated blood, red: oxygenated blood, purple: mix of deoxygenated and oxygenated blood.</p

Distribution of the different types of DILV hearts.

<p>Hearts are arranged by their type of ventriculoarterial connection with the position of the morphologically right ventricle in relation to the morphologically left ventricle. DOLV: double outlet left ventricle, DORV: double outlet right ventricle, LV: morphologically left ventricle, RV: morphologically right ventricle, VA: ventriculoarterial connection.</p

Ventricular relationships.

<p>Depicted is the morphologically left ventricle (grey circle) as seen from a superior position and the possible locations of the morphologically right ventricle (red ovals) along the anterior side of the morphologically left ventricle. The anterior side of the heart is divided in five parts (left/right and anterior/lateral) in intervals of 36°.</p

Evolution and Development of Ventricular Septation in the Amniote Heart

<div><p>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 elephants. The 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.</p></div

Development of chicken septum.

<p>(<b>A</b>) epicardium (→) infolding, located between OFT and AVcanal. (<b>B</b>) In situ hybridisation showing weakly positive Tbx5 of the RV and negative OFT with boundary (arrow). The atria are strongly positive. (<b>C</b>) more posterior section of the same embryo through folding septum (FS), the stronger left sided expression is evident, as is the septal band (+); boundary (> <) indicates FS. (<b>D-G</b>) 3D reconstruction with septum components and epicardial cushion. See also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106569#pone.0106569.s003" target="_blank">figure S2</a> for full animation and Fig. 6 for underlying sections, explaining the various components. (<b>H-L</b>) PEO quail-chicken chimeras. (<b>H, I</b>) anterior quail PEO(+liver) transplant, quail endothelial cells are exclusively present in FS and anterior free wall (<b>J-L</b>) posterior PEO (+liver) transplant with quail vascular profiles in IS (<b>J, K</b>) and right face of tricuspid orifice (<b>L</b>), but not in FS. (<b>K</b>) Several quail cells (arrows) in septal band (+), but FS does not harbor quail cells and remains negative (<b>K, L</b>). (<b>M-P</b>) DiI marking at HH17 of anterior myocardium surviving until HH28 and 31. (<b>M</b>) parts of the DiI patch (arrow) after survival to HH28 on left, (<b>N</b>) DiI on the right face and (<b>O</b>) DiI near the apex. (<b>P</b>) DiI inside the septum at HH31. Abbrev. as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0106569#pone-0106569-g002" target="_blank">Fig 2</a>. Others: AVC atrioventricular cushions; LA/LV left atrium and ventricle; RA/RV right atrium and ventricle; + septal band.</p

Index for the terminology used.

<p>The numbers refer to the ^superscripts in the Table.</p>1<p>. Combinations of aortic sac, truncus, conus and bulbus have been used to describe this segment. Conus and bulbus are usually myocardial, whereas aortic sac and truncus refer mostly to the vascular part. Septation from the vascular, semilunar valve and intracardiac levels is interchangeably referred to as either aorto-pulmonary septum or outflow tract (OFT) septum. The endocardial cushions in the proximal intracardiac part myocardialize through induction by neural crest cells forming the aorto-pulmonary or OFT septum. The distal part of the cushions is remodelled into semilunar valves that are separated by fibrous tissue between the orifices of the great arteries. In reptiles the aorto-pulmonary septum is branched and separates the two aortae and the pulmonary trunk. In mammals the distinction between proximal and distal endocardial cushions is inconspicuous.</p>2.<p>Bulboventricular fold, synonymous with the primary fold, between outflow and inlet portion of the primitive ventricle.</p>3.<p>Anterior (positional), primary (time-related) and folding (mechanistic, new in this paper) septum are synonymously used. The bulboventricular fold extends apically over the anterior surface of the heart and deepens to enclose epicardium and subepicardial tissue, thus forming an anteriorly located folding septum. The folding septum is considered to be homologous to the reptilian horizontal septum, which is also called the muscular ridge (see for further synonyms ref 13).</p>4.<p>The apical trabecular septum develops from the coalescence of many trabeculations and does not show a clear demarcation with the folding septum or the inlet septum.</p>5.<p>The inlet septum in early stages of eventually completely septated hearts and in some reptiles (presence is species-dependent) is a dense muscular structure on the posterior wall of the ventricle without an infolding mechanism. In the current study we have clearly shown that the anterior margin of the inlet septum with the folding septum is formed by the septal band or trabecula septomarginalis. In earlier literature the septal band has been described as the posterior margin of the primary (or folding) septum.</p>6.<p>The superior and inferior atrioventricular endocardial cushions fuse in the midline. In the central part the cushions are remodelled into fibrous (membranous) tissue that becomes part of the fibrous heart skeleton. Part of this forms the membranous septum which is located between right atrium and outflow of the left ventricle (atrio-ventricular component) and the remainder between RV and LV (interventricular component).This tissue is obliquely embedded in both the atrial and ventricular septa and as such is sometimes referred to as atrioventricular septum.</p><p>Index for the terminology used.</p

Evolution and septation of the heart.

<p>A. Evolution of hearts in higher vertebrates. Archosaurs (crocodilians, birds) and mammals independently evolved complete ventricular septation. Birds and mammals have lost either a left (lAo) or right (rAo) aorta. The horizontal (hs) and vertical septum (vs) are schematically indicated, together with the pulmonary trunk (Pt). The evolutionary tree is based on ref (2). B. Septum components in the human heart. Right face of the septum in a human heart after opening the right ventricle (RV), with inlet and folding components. Dissection line of the RV free wall in pink. Abbreviations: FS folding septum, IS inlet septum; MB moderator band; Pu pulmonary semilunar valve leaflets; SB septal band; TV anterior tricuspid valve leaflet with chordae tendineae (arrows) connected to SB and IS.; VIF ventriculo-infundibular fold. Fig. courtesy dr. L. Houyel.</p