Yap is required for ependymal integrity and is suppressed in LPA-induced hydrocephalus.,Nature Communications

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Yap is required for ependymal integrity and is suppressed in LPA-induced hydrocephalus.
Nature Communications ( IF 14.7 ) Pub Date : 2016-Jan-12 , DOI: 10.1038/ncomms10329
Raehee Park _{1,

2} , Uk Yeol Moon _{1,

2} , Jun Young Park _{1,

2} , Lucinda J Hughes _{1,

3} , Randy L Johnson ₄ , Seo-Hee Cho _{1,

2} , Seonhee Kim _{1,

2}

Affiliation

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.

中文翻译：

Yap 是室管膜完整性所必需的，并且在 LPA 诱导的脑积水中受到抑制。

沿导水管的室管膜细胞的及时生成和正常成熟对于防止第三脑室和第四脑室之间的物理阻塞以及胎儿非交通性脑积水的发展至关重要。我们的研究确定了 Yap（进化上保守的 Hippo 通路的下游效应器）作为沿导水管心室壁生成发育控制的室管膜细胞的中央调节器。 Yap 功能对于祖细胞的正常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）（Yap 的上游调节因子，可导致胎儿出血性脑积水）引发的损伤信号，会解除发育中导水管中 Yap 的调节。 LPA 暴露会导致顶端脚处 N-钙粘蛋白浓度的损失，这可以通过强制 Yap 表达部分恢复，并且通过磷模拟 Yap 更有效地恢复。这些结果揭示了 Yap 在正常发育期间和胎儿脑损伤后保持组织连接方面的新功能。

更新日期：2016-01-15

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