Poelmann Robert E, Gittenberger-de Groot Adriana C, Vicente-Steijn Rebecca, Wisse Lambertus J, Bartelings Margot M, Everts Sonja, Hoppenbrouwers Tamara, Kruithof Boudewijn P T, Jensen Bjarke, de Bruin Paul W, Hirasawa Tatsuya, Kuratani Shigeru, Vonk Freek, van de Put Jeanne M M S, de Bakker Merijn A, Richardson Michael K
Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; Institute of Biology Leiden (IBL), Leiden University, Sylvius Laboratory, Leiden, The Netherlands.
Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
PLoS One. 2014 Sep 5;9(9):e106569. doi: 10.1371/journal.pone.0106569. eCollection 2014.
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.
在心脏发生过程中，覆盖心肌管表面的心外膜被认为具有对从七鳃鳗到哺乳动物等脊椎动物正常心脏发育至关重要的多种功能。我们研究了心外膜在部分和完全分隔物种心室发育中的新功能。这些物种包括爬行动物、鸟类和哺乳动物。成年海龟、蜥蜴和蛇有一个复杂的心室，有三个腔，由水平和垂直隔膜部分分隔。然而，起源相隔约1亿年的鳄鱼、鸟类和哺乳动物有完全分隔的左心室和右心室，这是趋同进化的一个明显例子。在特定的胚胎阶段，这些物种在发育上表现出相似性，促使我们研究心外膜参与的潜在机制。早期胚胎的原始心室通过前室壁的折叠和融合而分隔，将心外膜困在其核心。这种折叠隔膜在爬行动物中发育为水平隔膜，在其他分类群中发育为室间隔的前部。通过心室表面的DiI标记证实了折叠机制。通过将胚胎鹌鹑原心外膜器官移植到鸡宿主中来研究心外膜来源细胞的捕获。在基因敲除小鼠和心外膜消融的鸡中研究心外膜参与减少的影响，导致隔膜形成减少甚至缺失。适当的折叠随后心室融合减少可能解释了大象中观察到的深室间裂。垂直隔膜在大多数爬行动物中不明显，除了鳄鱼和蟒科动物，显然与入口隔膜同源。最终，各种隔膜成分合并形成完全分隔的心脏。在我们试图发现各种隔膜成分之间的同源性时，我们旨在阐明脊椎动物心脏这一部分的进化和发育，以及了解人类先天性心脏畸形中隔膜缺损的病因。
