Myofibrillogenesis in the developing zebrafish heart: A functional study of tnnt2.
Myofibrillogenesis in the developing zebrafish heart: A functional study of tnnt2.
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DOI：
10.1016/j.ydbio.2009.04.039
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发表时间：
2009-07-15
影响因子：
2.7
通讯作者：
Xu, Xiaolei
中科院分区：
文献类型：
--
作者：
Huang, Wei;Zhang, Ruilin;Xu, Xiaolei
由于缺乏对肌节基因在体内模型中的系统遗传学研究，人们提出了各种假说来解释肌节组装的分子过程。为了实现发展斑马鱼作为脊椎动物模型的目标，我们的特点是在发展中的斑马鱼心脏肌原纤维生成，并继续检查心肌肌钙蛋白T（tnnt 2）的功能。我们发现，在斑马鱼的心脏肌节组装开始从一个非横纹肌动蛋白纤维网络在膜周区域，而肌节肌球蛋白是独立组装成粗丝可变长度的细丝之前，整合到细丝网络。与最初对齐以形成较短周期性点并在稍后时间纵向扩展的Z盘相比，M线组装较晚并且具有恒定长度。耗尽全长tnnt 2破坏条纹的细丝和Z-机构，从而影响条纹的粗丝和M-线。相反，截短的C-末端肌钙蛋白复合物结合域不影响这些肌小节子结构的条纹，但导致心肌细胞的大小减少。总之，我们的数据表明，斑马鱼是一个有价值的体内模型，研究肌原纤维和肌节为基础的心脏疾病。
Various hypotheses have been proposed to explain the molecule processes of sarcomere assembly, partially due to the lack of systematic genetic studies of sarcomeric genes in an in vivo model. Towards the goal of developing zebrafish as a vertebrate model for this purpose, we characterized myofibrillogenesis in a developing zebrafish heart and went on to examine the functions of cardiac troponin T (tnnt2). We found that sarcomere assembly in zebrafish heart was initiated from a non-striated actin filament network at the perimembrane region, whereas sarcomeric myosin is independently assembled into thick filaments of variable length before integrating into the thin filament network. Compared to Z-discs that are initially aligned to form shorter periodic dots and expanded longitudinally at a later time, M-lines assemble later and have a constant length. Depletion of full-length tnnt2 disrupted the striation of thin filaments and Z-bodies, which sequentially affects the striation of thick filaments and M-lines. Conversely, truncation of a C-terminal troponin complex-binding domain did not affect the striation of these sarcomere sub-structures, but resulted in reduced cardiomyocyte size. In summary, our data indicates that zebrafish are a valuable in vivo model for studying both myofibrillogenesis and sarcomere-based cardiac diseases.
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