Chamber formation and morphogenesis in the developing mammalian heart
Chamber formation and morphogenesis in the developing mammalian heart
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DOI：
10.1006/dbio.2000.9753
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发表时间：
2000-07-15
影响因子：
2.7
通讯作者：
Moorman, AFM
中科院分区：
文献类型：
--
作者：
Christoffels, VM;Habets, PEMH;Moorman, AFM
在这项研究中，我们挑战了普遍接受的观点，即心腔是由沿着线性和环状心管的前后轴排列的节段性原基阵列形成的。我们追踪了心钠素、肌浆网钙ATPase、Chisel、IRX5、IRX4、肌球蛋白轻链2v和β-肌球蛋白重链基因表达的空间模式，并将这些基因与形态发生相关。基于这些模式，我们提出了胚胎心脏心腔形成的两步模型。首先，形成一个线形心脏，它由“原始”心肌组成，但在其前后和背腹轴上表现出表型和基因表达的两极。第二，特殊的室腔心肌位于线性心管的腹面，而不同的左、右心房心肌在背外侧表面形成更接近尾部的位置。循环的过程使这些原始腔室对齐，使它们面向外曲率。内曲心肌，以及流入道、房室管和流出道的心肌，保留了最初在线性心管心肌中发现的分子特征。在背腹轴的Hand1，前后轴的Irx4和Tbx5，以及区分初级和腔室心肌的IRX5的表达模式中，可以看到控制形成心脏分区的不同转录程序的证据。(C)2000年学术出版社。
In this study we challenge the generally accepted view that cardiac chambers form from an array of segmental primordia arranged along the anteroposterior axis of the linear and looping heart tube. We traced the spatial pattern of expression of genes encoding atrial natriuretic factor, sarcoplasmic reticulum calcium ATPase, Chisel, Irx5, Irx4, myosin light chain 2v, and beta-myosin heavy chain and related these to morphogenesis. Based on the patterns we propose a two-step model for chamber formation in the embryonic heart. First, a linear heart forms, which is composed of "primary" myocardium that nonetheless shows polarity in phenotype and gene expression along its anteroposterior and dorsoventral axes. Second, specialized ventricular chamber myocardium is specified at the ventral surface of the linear heart tube, while distinct left and right atrial myocardium forms more caudally on laterodorsal surfaces. The process of looping aligns these primordial chambers such that they face the outer curvature. Myocardium of the inner curvature, as well as that of inflow tract, atrioventricular canal, and outflow tract, retains the molecular signature originally found in linear heart tube myocardium. Evidence for distinct transcriptional programs which govern compartmentalization in the forming heart is seen in the patterns of expression of Hand1 for the dorsoventral axis, Irx4 and Tbx5 for the anteroposterior axis, and Irx5 for the distinction between primary and chamber myocardium. (C) 2000 Academic Press.