Ya J, van den Hoff M J, de Boer P A, Tesink-Taekema S, Franco D, Moorman A F, Lamers W H
Department of Anatomy and Embryology, Academic Medical Center, University of Amsterdam, The Netherlands.
Circ Res. 1998 Mar 9;82(4):464-72. doi: 10.1161/01.res.82.4.464.
The outflow tract (OFT) provides the structural components forming the ventriculoarterial connection. The prevailing concept that this junction "rotates" to acquire its definitive topography also requires a concept of "counterrotation" and is difficult to reconcile with cell-marking studies. Rats between 10 embryonic days (EDs) and 2 postnatal days were stained immunohistochemically and by in situ hybridization. DNA replication was determined by incorporation of bromodeoxyuridine and apoptosis by the annexin V binding and terminal deoxynucleotidyl transferase-mediated dUTP-X nick end labeling (TUNEL) assays. Starting at ED12, cardiomyocytes in the distal (truncal) part of the OFT begin to shed their myocardial phenotype without proceeding into apoptosis, suggesting transdifferentiation. Myocardial regression is most pronounced on the dextroposterior side and continues until after birth, as revealed by the disappearance of the myocardial cuff surrounding the coronary roots and semilunar sinuses and by the establishment of fibrous continuity between mitral and aortic semilunar valves. Fusion of the endocardial ridges of the truncus on late ED13 is accompanied by the organization of alpha-smooth muscle actin-and nonmuscle myosin heavy chain-positive myofibroblasts into a central whorl and the appearance of the semilunar valve anlagen at their definitive topographical position within the proximal portion of the truncus. After fusion of the proximal (conal) portion of the endocardial ridges, many of the resident myofibroblasts undergo apoptosis and are replaced by cardiomyocytes. The distal myocardial boundary of the OFT is not a stable landmark but moves proximally over the spiraling course of the aortic and pulmonary routes, so that the semilunar valves develop at their definitive topographic position. After septation, the distal boundary of the OFT continues to regress, particularly in its subaortic portion. The myocardializing conus septum, on the other hand, becomes largely incorporated into the right ventricle. These opposite developments account for the pronounced asymmetry of the subaortic and subpulmonary outlets in the formed heart.
流出道（OFT）提供了构成心室动脉连接的结构成分。目前认为该连接处“旋转”以获得其最终形态的观点还需要“反向旋转”的概念，并且难以与细胞标记研究相协调。对10个胚胎日（EDs）至出生后2天的大鼠进行免疫组织化学染色和原位杂交。通过掺入溴脱氧尿苷来确定DNA复制，并通过膜联蛋白V结合和末端脱氧核苷酸转移酶介导的dUTP-X缺口末端标记（TUNEL）测定法来检测细胞凋亡。从胚胎第12天开始，OFT远端（干段）的心肌细胞开始丧失其心肌表型，但未进入凋亡阶段，提示发生了转分化。心肌消退在右后外侧最为明显，并持续至出生后，这可通过围绕冠状动脉根部和半月窦的心肌袖口消失以及二尖瓣和主动脉半月瓣之间纤维连续性的建立来证明。胚胎第13天晚期，动脉干的心内膜嵴融合，同时α-平滑肌肌动蛋白和非肌肉肌球蛋白重链阳性的肌成纤维细胞组织成中央螺旋，并在动脉干近端的最终位置出现半月瓣原基。心内膜嵴近端（圆锥段）融合后，许多驻留的肌成纤维细胞发生凋亡，并被心肌细胞取代。OFT的远端心肌边界不是一个稳定的标志，而是在主动脉和肺动脉路径的螺旋过程中向近端移动，从而使半月瓣在其最终位置发育。分隔后，OFT的远端边界继续消退，尤其是在其主动脉下部分。另一方面，心肌化的圆锥间隔大部分融入右心室。这些相反的发育过程导致了已形成心脏中主动脉下和肺动脉下出口的明显不对称。
