A retrospective clonal analysis of the myocardium reveals two phases of clonal growth in the developing mouse heart
A retrospective clonal analysis of the myocardium reveals two phases of clonal growth in the developing mouse heart
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DOI：
10.1242/dev.00580
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发表时间：
2003-08-01
期刊：
影响因子：
4.6
通讯作者：
Buckingham, ME
中科院分区：
文献类型：
--
作者：
Meilhac, SM;Kelly, RG;Buckingham, ME
调节心脏形成的关键分子已被确定；然而，心脏形态发生的机制在细胞水平上仍然知之甚少。我们采用了一种遗传方法，基于 nlaacZ 报告基因对 α-心肌肌动蛋白基因的靶向，可以对小鼠胚胎中的心肌细胞进行回顾性克隆分析。罕见的基因内重组事件导致β-半乳糖苷酶阳性心肌细胞的克隆。对不同发育阶段的克隆的分析表明，心肌细胞及其前体遵循增殖生长模式，而不是干细胞模式，具有初始分散阶段，随后是连贯细胞生长。细胞簇沿着心管的静脉-动脉轴分散。相干生长是局部定向的，具有对应于簇的伸长的主轴和形成次轴的细胞行。主轴和次轴之间的角度变化，表明生长方向的独立事件。在后期，随着心室壁增厚，楔形簇穿过心室壁并包含彼此成渐进角度的成排细胞。心肌的细胞组织似乎预示着肌纤维的结构。我们讨论了我们所描述的心肌细胞生长的特征如何成为心管形成及其随后的区域扩张的基础。
Key molecules which regulate the formation of the heart have been identified; however, the mechanism of cardiac morphogenesis remains poorly understood at the cellular level. We have adopted a genetic approach, which permits retrospective clonal analysis of myocardial cells in the mouse embryo, based on the targeting of an nlaacZ reporter to the alpha-cardiac actin gene. A rare intragenic recombination event leads to a clone of beta-galactosidase-positive myocardial cells. Analysis of clones at different developmental stages demonstrates that myocardial cells and their precursors follow a proliferative mode of growth, rather than a stem cell mode, with an initial dispersive phase, followed by coherent cell growth. Clusters of cells are dispersed along the venous-arterial axis of the heart tube. Coherent growth is oriented locally, with a main axis, which corresponds to the elongation of the cluster, and rows of cells, which form secondary axes. The angle between the primary and secondary axes varies, indicating independent events of growth orientation. At later stages, as the ventricular wall thickens, wedge shaped clusters traverse the wall and contain rows of cells at a progressive angle to each other. The cellular organisation of the myocardium appears to prefigure myofibre architecture. We discuss how the characteristics of myocardial cell growth, which we describe, underlie the formation of the heart tube and its subsequent regionalised expansion.