Tbx20 regulation of cardiac cell proliferation and lineage specialization during embryonic and fetal development in vivo.
Tbx20 regulation of cardiac cell proliferation and lineage specialization during embryonic and fetal development in vivo.
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DOI：
10.1016/j.ydbio.2011.12.034
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发表时间：
2012-03-01
影响因子：
2.7
通讯作者：
Yutzey KE
中科院分区：
文献类型：
--
作者：
Chakraborty S;Yutzey KE
人类TBX 20功能获得性突变与先天性心脏畸形和心肌缺损相关。然而，在心腔发育和成熟过程中增加Tbx 20功能的影响以前尚未报道。产生CAG-CAT-Tbx 20转基因小鼠，用于在发育中的心脏的心肌谱系中Cre依赖性诱导Tbx 20。β MHCCre介导的Tbx 20在胎儿心室心肌细胞中的过表达导致致密心肌厚度增加，诱导心肌细胞增殖，以及在胚胎第14.5天（E）增加Bmp 10和pSmad 1/5/8的表达。β MHCCre介导的Tbx 20过表达还导致整个心室肌中心脏传导系统（CCS）基因Tbx 5、Cx40和Cx43的表达增加。相反，在胚胎心脏中，Nkx2.5Cre介导的Tbx 20过表达导致心肌细胞增殖减少，细胞周期抑制剂p21 CIP 1表达增加，以及在E9.5时Tbx 2、Tbx 5和N-myc 1表达减少，同时磷酸化ERK 1/2表达减少。总之，这些分析表明，Tbx 20差异调节细胞增殖和胚胎与胎儿心肌细胞的心脏谱系特化。在E14.5诱导pSmad 1/5/8和在E9.5抑制dpERK表达与Tbx 20对这些通路的选择性调节一致，这些通路与对心肌细胞增殖的阶段特异性作用相关。总之，这些体内数据支持Tbx 20在心脏发育的胚胎和胎儿阶段调节心肌细胞谱系成熟和细胞增殖的不同功能。
TBX20 gain-of-function mutations in humans are associated with congenital heart malformations and myocardial defects. However the effects of increased Tbx20 function during cardiac chamber development and maturation have not been reported previously. CAG-CAT-Tbx20 transgenic mice were generated for Cre-dependent induction of Tbx20 in myocardial lineages in the developing heart. βMHCCre-mediated overexpression of Tbx20 in fetal ventricular cardiomyocytes results in increased thickness of compact myocardium, induction of cardiomyocyte proliferation, and increased expression of Bmp10 and pSmad1/5/8 at embryonic day (E) 14.5. βMHCCre-mediated Tbx20 overexpression also leads to increased expression of cardiac conduction system (CCS) genes Tbx5, Cx40, and Cx43 throughout the ventricular myocardium. In contrast, Nkx2.5Cre mediated overexpression of Tbx20 in the embryonic heart results in reduced cardiomyocyte proliferation, increased expression of a cell cycle inhibitor, p21CIP1, and decreased expression of Tbx2, Tbx5, and N-myc1 at E9.5, concomitant with decreased phospho-ERK1/2 expression. Together, these analyses demonstrate that Tbx20 differentially regulates cell proliferation and cardiac lineage specification in embryonic versus fetal cardiomyocytes. Induction of pSmad1/5/8 at E14.5 and inhibition of dpERK expression at E9.5 are consistent with selective Tbx20 regulation of these pathways in association with stage-specific effects on cardiomyocyte proliferation. Together, these in vivo data support distinct functions for Tbx20 in regulation of cardiomyocyte lineage maturation and cell proliferation at embryonic and fetal stages of heart development.
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影响因子：
15.9
作者：
Aanhaanen, Wim T. J.;Boukens, Bastiaan J. D.;Christoffels, Vincent M.
通讯作者：
Christoffels, Vincent M.
影响因子：
2.5
作者：
Christoffels, VM;Hoogaars, WMH;Campione, M
通讯作者：
Campione, M
影响因子：
2.5
作者：
Lincoln, J;Alfieri, CM;Yutzey, KE
通讯作者：
Yutzey, KE
影响因子：
20.1
作者：
Lai, Donna;Liu, Xifu;Harvey, Richard P.
通讯作者：
Harvey, Richard P.
影响因子：
4.6
作者：
Chakraborty, Santanu;Cheek, Jonathan;Yutzey, Katherine E.
通讯作者：
Yutzey, Katherine E.