Wnt6 signaling regulates heart muscle development during organogenesis
Wnt6 signaling regulates heart muscle development during organogenesis
复制标题
DOI：
10.1016/j.ydbio.2008.08.032
复制
发表时间：
2008-11-15
影响因子：
2.7
通讯作者：
Hoppler, Stefan
中科院分区：
文献类型：
--
作者：
Lavery, Danielle L.;Martin, Jennifer;Hoppler, Stefan
在原肠胚形成期间诱导具有心脏形成潜力的中胚层组织（心源性中胚层）。这种心源性中胚层后来分化成心肌组织（心肌）和非肌肉性心脏组织。已知Wnt/β-连环蛋白信号传导的抑制是诱导心源性中胚层早期所需的：然而，抑制Writ信号本身的身份仍然难以捉摸。我们已经在非洲爪蟾中鉴定出Wnt 6作为内源性Writ信号，其在靠近发育中的心脏的组织中以及之后在发育中的心脏内表达。我们的功能丧失实验表明，胚胎中需要Wnt 6功能来防止异常大的心肌发育。然而，我们发现，Wnt 6并不需要如预期在原肠胚阶段，但后来在器官发生阶段之前的心源性中胚层细胞开始分化成心肌（心肌）。我们的功能获得实验表明，Wnt 6和激活的经典Wnt/β-连环蛋白信号能够在这些相对较晚的发育阶段限制心肌发育。Wilt信号传导的这种抑制作用最初是通过抑制心源性转录因子介导的，因为加塔功能的恢复可以挽救其他心源性转录因子和下游心肌分化基因的表达。(C)2008年爱思唯尔公司All rights reserved.
Mesodermal tissue with heart forming potential (cardiogenic mesoderm) is induced during gastrulation. This cardiogenic mesoderm later differentiates into heart muscle tissue (myocardium) and non-muscular heart tissue. Inhibition of Wnt/beta-catenin signaling is known to be required early for induction of cardiogenic mesoderm: however, the identity of the inhibiting Writ signal itself is still elusive. We have identified Wnt6 in Xenopus as an endogenous Writ signal, which is expressed in tissues close to and later inside the developing heart. Our loss-of-function experiments show that Wnt6 function is required in the embryo to prevent development of an abnormally large heart muscle. We find, however, that Wnt6 is not required as expected during gastrulation stages, but later during organogenesis stages just before cells of the cardiogenic mesoderm begin to differentiate into heart muscle (myocardium). Our gain-of-function experiments show that Wnt6 and also activated canonical Wnt/beta-catenin signaling are capable of restricting heart muscle development at these relatively late stages of development. This repressive role of Wilt signaling is mediated initially via repression of cardiogenic transcription factors, since reinstatement of GATA function can rescue expression of other cardiogenic transcription factors and downstream cardiomyogenic differentiation genes. (C) 2008 Elsevier Inc. All rights reserved.