Characterization and In Vivo Pharmacological Rescue of a Wnt2-Gata6 Pathway Required for Cardiac Inflow Tract Development
Characterization and In Vivo Pharmacological Rescue of a Wnt2-Gata6 Pathway Required for Cardiac Inflow Tract Development
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DOI：
10.1016/j.devcel.2010.01.008
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发表时间：
2010-02-16
影响因子：
11.8
通讯作者：
Morrisey, Edward E.
中科院分区：
文献类型：
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作者：
Tian, Ying;Yuan, Lijun;Morrisey, Edward E.
对心脏后极形态发生的分子机制知之甚少。在这里，我们表明，Wnt 2是专门在发展中的流入道中胚层，产生部分的心房和房室管。Wnt 2的缺失导致心脏后极的发育缺陷，导致类似于人类先天性心脏综合征完全共同房室管的表型。Wnt 2（-/-）突变体中后第二心脏区祖细胞的数量和增殖减少。此外，这些缺陷可以通过Gsk-3 β的药理学抑制以时间限制的方式被挽救。我们还表明，Wnt 2与Gata 6在前馈转录环中起作用，以调节后心脏发育。这些数据揭示了调节心脏后中胚层的分子途径，并证明了由Wnt信号传导丢失引起的心血管缺陷可以在体内被挽救。
Little is understood about the molecular mechanisms underlying the morphogenesis of the posterior pole of the heart. Here we show that Wnt2 is expressed specifically in the developing inflow tract mesoderm, which generates portions of the atria and atrioventricular canal. Loss of Wnt2 results in defective development of the posterior pole of the heart, resulting in a phenotype resembling the human congenital heart syndrome complete common atrio-ventricular canal. The number and proliferation of posterior second heart field progenitors is reduced in Wnt2(-/-) mutants. Moreover, these defects can be rescued in a temporally restricted manner through pharmacological inhibition of Gsk-3 beta. We also show that Wnt2 works in a feedforward transcriptional loop with Gata6 to regulate posterior cardiac development. These data reveal a molecular pathway regulating the posterior cardiac mesoderm and demonstrate that cardiovascular defects caused by loss of Wnt signaling can be rescued pharmacologically in vivo.