Goetz Sarah C, Brown Daniel D, Conlon Frank L
Carolina Cardiovascular Biology Center, 5109 Neuroscience Research Building, Chapel Hill, NC 27599-7126, USA.
Development. 2006 Jul;133(13):2575-84. doi: 10.1242/dev.02420. Epub 2006 May 25.
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.
尽管TBX5在正常发育和疾病中至关重要，但对于TBX5在胚胎心脏中发挥作用的机制，我们所知相对较少。我们目前的研究表明，TBX5对于控制胚胎心脏细胞周期的时长是必需的，TBX5的缺失会导致心脏细胞周期在G1期晚期或S期早期停滞。通过缺失TBX5来阻断细胞周期进程会导致心脏细胞数量减少、心脏分化程序的时间改变、心脏肌节形成缺陷，最终导致心脏程序性细胞死亡。在这些研究中，我们还证实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，TBX5足以决定胚胎心脏细胞周期的时长和心脏分化程序的时间。因此，这些研究确立了TBX5在调节心脏细胞周期进程中的作用。
