Yap is required for ependymal integrity and is suppressed in LPA-induced hydrocephalus.
Yap is required for ependymal integrity and is suppressed in LPA-induced hydrocephalus.
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DOI：
10.1038/ncomms10329
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发表时间：
2016-01-12
影响因子：
16.6
通讯作者：
Kim S
中科院分区：
文献类型：
--
作者：
Park R;Moon UY;Park JY;Hughes LJ;Johnson RL;Cho SH;Kim S
室管膜细胞沿着导水管的及时生成和正常成熟对于防止第三和第四脑室之间的物理性堵塞和胎儿非交通性脑积水的发展至关重要。我们的研究确定了雅普，下游效应的进化保守的河马途径，作为一个中央调节器产生发育控制室管膜细胞沿着心室衬里的水管。雅普功能对于祖细胞的适当增殖和室管膜前体细胞的顶端附着是必需的。重要的是，由溶血磷脂酸（LPA）启动的损伤信号，一种可导致胎儿出血性脑积水的雅普的上游调节因子，在发育中的导水管中解除雅普的调节。LPA暴露导致N-钙粘蛋白浓度的损失，在顶端的endfeet，这可以部分恢复强制雅普的表达和更有效的磷酸化模拟雅普。这些结果揭示了雅普在正常发育过程中和胎儿脑损伤后保留组织连接的新功能。 覆盖脑室表面的室管膜细胞层的衰竭可导致胎儿脑积水。Park等揭示了Hippo途径基因雅普在室管膜细胞产生中的作用，并显示在脑积水模型中观察到雅普的抑制。
Timely generation and normal maturation of ependymal cells along the aqueduct are critical for preventing physical blockage between the third and fourth ventricles and the development of fetal non-communicating hydrocephalus. Our study identifies Yap, the downstream effector of the evolutionarily conserved Hippo pathway, as a central regulator for generating developmentally controlled ependymal cells along the ventricular lining of the aqueduct. Yap function is necessary for proper proliferation of progenitors and apical attachment of ependymal precursor cells. Importantly, an injury signal initiated by lysophosphatidic acid (LPA), an upstream regulator of Yap that can cause fetal haemorrhagic hydrocephalus, deregulates Yap in the developing aqueduct. LPA exposure leads to the loss of N-cadherin concentrations at the apical endfeet, which can be partially restored by forced Yap expression and more efficiently by phosphomimetic Yap. These results reveal a novel function of Yap in retaining tissue junctions during normal development and after fetal brain injury. Failure of the ependymal cell layer that lines the ventricular surfaces of the brain can result in fetal hydrocephalus. Park et al. reveal a role for the Hippo pathway gene Yap in the generation of ependymal cells, and show that suppression of Yap is observed in a model of hydrocephalus.