Department of Anatomy, Embryology & Physiology, Academic Medical Center, Amsterdam, The Netherlands.
Am J Med Genet A. 2014 Jun;164A(6):1347-71. doi: 10.1002/ajmg.a.35896. Epub 2013 Apr 30.
Molecular and genetic studies around the turn of this century have revolutionized the field of cardiac development. We now know that the primary heart tube, as seen in the early embryo contains little more than the precursors for the left ventricle, whereas the precursor cells for the remainder of the cardiac components are continuously added, to both the venous and arterial pole of the heart tube, from a single center of growth outside the heart. While the primary heart tube is growing by addition of cells, it does not show significant cell proliferation, until chamber differentiation and expansion starts locally in the tube, by which the chambers balloon from the primary heart tube. The transcriptional repressors Tbx2 and Tbx3 locally repress the chamber-specific program of gene expression, by which these regions are allowed to differentiate into the distinct components of the conduction system. Molecular genetic lineage analyses have been extremely valuable to assess the distinct developmental origin of the various component parts of the heart, which currently can be unambiguously identified by their unique molecular phenotype. Despite the enormous advances in our knowledge on cardiac development, even the most common congenital cardiac malformations are only poorly understood. The challenge of the newly developed molecular genetic techniques is to unveil the basic gene regulatory networks underlying cardiac morphogenesis.
本世纪初的分子和遗传学研究彻底改变了心脏发育领域。我们现在知道，早期胚胎中的初级心管中几乎只包含左心室的前体，而心脏其余部分的前体细胞则不断地从心脏外部的一个单一生长中心添加到心管的静脉和动脉极。当初级心管通过细胞添加而生长时，它不会显示出明显的细胞增殖，直到腔室分化和扩张开始在管内局部进行，此时腔室从初级心管中膨胀。转录抑制因子 Tbx2 和 Tbx3 局部抑制腔室特异性基因表达程序，使这些区域能够分化为传导系统的不同组成部分。分子遗传谱系分析对于评估心脏各个组成部分的独特发育起源非常有价值，目前可以通过其独特的分子表型来明确识别。尽管我们在心脏发育方面取得了巨大的进展，但即使是最常见的先天性心脏畸形也知之甚少。新开发的分子遗传学技术的挑战在于揭示心脏形态发生的基本基因调控网络。
