Distinct phases of Wnt/β-catenin signaling direct cardiomyocyte formation in zebrafish.
Distinct phases of Wnt/β-catenin signaling direct cardiomyocyte formation in zebrafish.
复制标题
DOI：
10.1016/j.ydbio.2011.10.032
复制
发表时间：
2012-01-15
影响因子：
2.7
通讯作者：
Waxman JS
中科院分区：
文献类型：
--
作者：
Dohn TE;Waxman JS
正常的心脏形成需要经典Wnt/β-连环蛋白（Wnt）信号传导的反复阶段。了解Wnt信号传导在体内指导心肌细胞（CM）形成的机制对于能够在体外精确指导干细胞分化的CM至关重要。在这里，我们调查的作用Wnt信号在斑马鱼CM形成热休克诱导的转基因，增加和减少Wnt信号。我们发现，有三个阶段，在此期间，CM的形成是敏感的Wnt信号的调制，通过第一个24小时的发展。除了先前公认的作用Wnt信号在中胚层规范和在前心中胚层，我们发现了一个以前未被认识到的作用，在CM分化过程中，Wnt信号是必要的，足以促进额外的心房细胞的分化。我们还扩展了以前的研究中的作用Wnt信号在中胚层规范和前心中胚层。重要的是，在前心脏中胚层，我们定义了一个新的机制，其中Wnt信号足以防止CM分化，在抑制心脏祖细胞（CP）规范的建议的作用。CP不能分化似乎通过p53/Caspase-3独立机制导致细胞死亡。再加上一份报告，甚至更晚的作用Wnt信号在限制分化的心室CM的增殖，我们的研究结果表明，在斑马鱼发育的前3天，有四个不同的阶段，在此期间，CM是敏感的Wnt信号。
Normal heart formation requires reiterative phases of canonical Wnt/β-catenin (Wnt) signaling. Understanding the mechanisms by which Wnt signaling directs cardiomyocyte (CM) formation in vivo is critical to being able to precisely direct differentiated CMs from stem cells in vitro. Here, we investigate the roles of Wnt signaling in zebrafish CM formation using heat-shock inducible transgenes that increase and decrease Wnt signaling. We find that there are three phases during which CM formation is sensitive to modulation of Wnt signaling through the first 24 hours of development. In addition to the previously recognized roles for Wnt signaling during mesoderm specification and in the pre-cardiac mesoderm, we find a previously unrecognized role during CM differentiation where Wnt signaling is necessary and sufficient to promote the differentiation of additional atrial cells. We also extend the previous studies of the roles of Wnt signaling during mesoderm specification and in pre-cardiac mesoderm. Importantly, in pre-cardiac mesoderm we define a new mechanism where Wnt signaling is sufficient to prevent CM differentiation, in contrast to a proposed role in inhibiting cardiac progenitor (CP) specification. The inability of the CPs to differentiate appears to lead to cell death through a p53/Caspase-3 independent mechanism. Together with a report for an even later role for Wnt signaling in restricting proliferation of differentiated ventricular CMs, our results indicate that during the first 3 days of development in zebrafish there are four distinct phases during which CMs are sensitive to Wnt signaling.
登录
查看更多内容
DOI：
10.1038/jid.2008.445
发表时间：
2009-07
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Chien AJ;Conrad WH;Moon RT
通讯作者：
Moon RT
影响因子：
2.7
作者：
Blum, Yannick;Belting, Heinz-Georg;Affolter, Markus
通讯作者：
Affolter, Markus
DOI：
10.1126/science.1177350
发表时间：
2009-10-16
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Domian IJ;Chiravuri M;van der Meer P;Feinberg AW;Shi X;Shao Y;Wu SM;Parker KK;Chien KR
通讯作者：
Chien KR
影响因子：
46.9
作者：
Chen, Vincent C.;Stull, Robert;Joo, Daniel;Cheng, Xin;Keller, Gordon
通讯作者：
Keller, Gordon
DOI：
10.1073/pnas.0704044104
发表时间：
2007-06-26
影响因子：
11.1
作者：
Kwon, Chulan;Arnold, Joshua;Srivastava, Deepak
通讯作者：
Srivastava, Deepak