Hirschy Alain, Schatzmann Franziska, Ehler Elisabeth, Perriard Jean-Claude
Institute of Cell Biology, ETH Zurich-Hönggerberg, CH-8093 Zurich, Switzerland.
Dev Biol. 2006 Jan 15;289(2):430-41. doi: 10.1016/j.ydbio.2005.10.046. Epub 2005 Dec 9.
Cardiomyocytes are characterized by an extremely well-organized cytoarchitecture. We investigated its establishment in the developing mouse heart with particular reference to the myofibrils and the specialized types of cell-cell contacts, the intercalated discs (ICD). Early embryonic cardiomyocytes have a polygonal shape with cell-cell contacts distributed circumferentially at the peripheral membrane and myofibrils running in a random orientation in the sparse cytoplasm between the nucleus and the plasma membrane. During fetal development, the cardiomyocytes elongate, and the myofibrils become aligned. The restriction of the ICD components to the bipolar ends of the cells is a much slower process and is achieved for adherens junctions and desmosomes only after birth, for gap junctions even later. By quantifying the specific growth parameters of prenatal cardiomyocytes, we were able to identify a previously unknown fetal phase of physiological hypertrophy. Our results suggest (1) that myofibril alignment, bipolarization and ICD restriction happen sequentially in cardiomyocytes, and (2) that increase of heart mass in the embryo is not only achieved by hyperplasia alone but also by volume increase of the individual cardiomyocytes (hypertrophy). These observations help to understand the mechanisms that lead to the formation of a functional heart during development at a cellular level.
心肌细胞的特征是具有极其有序的细胞结构。我们研究了其在发育中的小鼠心脏中的形成过程,特别关注肌原纤维和特殊类型的细胞间连接——闰盘(ICD)。早期胚胎心肌细胞呈多边形,细胞间连接沿外周膜周向分布,肌原纤维在细胞核与质膜之间稀疏的细胞质中随机排列。在胎儿发育过程中,心肌细胞伸长,肌原纤维排列整齐。ICD 成分局限于细胞的两极是一个慢得多的过程,仅在出生后粘附连接和桥粒才实现这一过程,间隙连接则更晚。通过量化产前心肌细胞的特定生长参数,我们能够识别出一个以前未知的生理性肥大胎儿期。我们的结果表明:(1)在心肌细胞中,肌原纤维排列、两极化和 ICD 局限化是依次发生的;(2)胚胎心脏质量的增加不仅通过单纯的细胞增生实现,还通过单个心肌细胞的体积增大(肥大)实现。这些观察结果有助于在细胞水平上理解发育过程中导致功能性心脏形成的机制。