Sakabe Masahide, Matsui Hiroko, Sakata Hirokazu, Ando Katsumi, Yamagishi Toshiyuki, Nakajima Yuji
Department of Anatomy, Graduate School of Medicine, Osaka City University, Abenoku, Osaka, Japan.
Congenit Anom (Kyoto). 2005 Dec;45(4):107-18. doi: 10.1111/j.1741-4520.2005.00079.x.
ABSTRACT The heart is the first organ to form and function during development. In the pregastrula chick embryo, cells contributing to the heart are found in the postero-lateral epiblast. During the pregastrula stages, interaction between the posterior epiblast and hypoblast is required for the anterior lateral plate mesoderm (ALM) to form, from which the heart will later develop. This tissue interaction is replaced by an Activin-like signal in culture. During gastrulation, the ALM is committed to the heart lineage by endoderm-secreted BMP and subsequently differentiates into cardiomyocyte. The right and left precardiac mesoderms migrate toward the ventral midline to form the beating primitive heart tube. Then, the heart tube generates a right-side bend, and the d-loop and presumptive heart segments begin to appear segmentally: outflow tract (OT), right ventricle, left ventricle, atrioventricular (AV) canal, atrium and sinus venosus. T-box transcription factors are involved in the formation of the heart segments: Tbx5 identifies the left ventricle and Tbx20 the right ventricle. After the formation of the heart segments, endothelial cells in the OT and AV regions transform into mesenchyme and generate valvuloseptal endocardial cushion tissue. This phenomenon is called endocardial EMT (epithelial-mesenchymal transformation) and is regulated mainly by BMP and TGFbeta. Finally, heart septa that have developed in the OT, ventricle, AV canal and atrium come into alignment and fuse, resulting in the completion of the four-chambered heart. Altered development seen in the cardiogenetic process is involved in the pathogenesis of congenital heart defects. Therefore, understanding the molecular nature regulating the 'nodal point' during heart development is important in order to understand the etiology of congenital heart defects, as well as normal heart development.
摘要 心脏是发育过程中第一个形成并开始发挥功能的器官。在原肠胚形成前的鸡胚中，形成心脏的细胞位于后外侧上胚层。在原肠胚形成前阶段，后上胚层与下胚层之间的相互作用对于前外侧板中胚层（ALM）的形成是必需的，心脏随后将从该中胚层发育而来。在培养过程中，这种组织相互作用被一种激活素样信号所取代。在原肠胚形成期间，内胚层分泌的骨形态发生蛋白（BMP）使ALM定向分化为心脏谱系，随后分化为心肌细胞。左右心脏前中胚层向腹侧中线迁移，形成跳动的原始心管。然后，心管产生右侧弯曲，d环和假定的心脏节段开始按节段出现：流出道（OT）、右心室、左心室、房室（AV）管、心房和静脉窦。T盒转录因子参与心脏节段的形成：Tbx5识别左心室，Tbx20识别右心室。心脏节段形成后，OT和AV区域的内皮细胞转化为间充质，并产生瓣膜间隔心内膜垫组织。这种现象称为心内膜上皮-间充质转化（EMT），主要受BMP和转化生长因子β（TGFβ）调节。最后，在OT、心室、AV管和心房中发育的心脏隔膜对齐并融合，导致四腔心形成完成。心脏发生过程中出现的发育改变与先天性心脏缺陷的发病机制有关。因此，了解心脏发育过程中调节“节点”的分子本质对于理解先天性心脏缺陷的病因以及正常心脏发育都很重要。
