TBX5 is required for embryonic cardiac cell cycle progression
TBX5 is required for embryonic cardiac cell cycle progression
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DOI：
10.1242/dev.02420
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发表时间：
2006-07-01
期刊：
影响因子：
4.6
通讯作者：
Conlon, Frank L.
中科院分区：
文献类型：
--
作者：
Goetz, Sarah C.;Brown, Daniel D.;Conlon, Frank L.
尽管TBX 5在正常发育和疾病中至关重要，但对TBX 5在胚胎心脏中发挥作用的机制知之甚少。我们目前的研究表明，TBX 5是必要的，以控制胚胎心脏细胞周期的长度，与TBX 5的耗竭导致心脏细胞周期停滞在晚期G（1）-或早期S-期。通过TBX 5耗竭阻断细胞周期进程导致心脏细胞数量减少、心脏分化程序的时序改变、心脏肌节形成缺陷，并最终导致心脏程序性细胞死亡。在这些研究中，我们还证实了终末分化的心肌细胞保留了进行细胞分裂的能力。我们进一步表明，TBX 5是足以确定胚胎心脏细胞周期的长度和心脏分化程序的时间。因此，这些研究确立了TBX 5在调节心脏细胞周期进程中的作用。
Despite the critical importance of TBX5 in normal development and disease, relatively little is known about the mechanisms by which TBX5 functions in the embryonic heart. Our present studies demonstrate that TBX5 is necessary to control the length of the embryonic cardiac cell cycle, with depletion of TBX5 leading to cardiac cell cycle arrest in late G(1)- or early S-phase. Blocking cell cycle progression by TBX5 depletion leads to a decrease in cardiac cell number, an alteration in the timing of the cardiac differentiation program, defects in cardiac sarcomere formation, and ultimately, to cardiac programmed cell death. In these studies we have also established that terminally differentiated cardiomyocytes retain the capacity to undergo cell division. We further show that TBX5 is sufficient to determine the length of the embryonic cardiac cell cycle and the timing of the cardiac differentiation program. Thus, these studies establish a role for TBX5 in regulating the progression of the cardiac cell cycle.