Yap/Taz are required for establishing the cerebellar radial glia scaffold and proper foliation

Yap/Taz是建立小脑放射状胶质细胞支架和正常叶状结构所必需的。

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作者:Lucinda J Hughes,Raehee Park,Min Jung Lee,Bethany K Terry,David J Lee,Hansol Kim,Seo-Hee Cho,Seonhee Kim

Abstract

Yap/Taz are well-established downstream effectors of the Hippo pathway, known to regulate organ size by directing proliferation and apoptosis. Although the functions of Yap/Taz have been extensively studied, little is known about their role in brain development. Here, through genetic ablation, we show that Yap/Taz are required for cerebellar morphogenesis. Yap/Taz deletion in neural progenitors causes defects in secondary fissure formation, leading to abnormal folia development. Although they seemed very likely to serve an important function in the development of cerebellar granule cell precursors, Yap/Taz are dispensable for their proliferation. Furthermore, Yap/Taz loss does not rescue the medulloblastoma phenotype caused by constitutively active Smoothened. Importantly, Yap/Taz are highly expressed in radial glia and play a crucial role in establishing the radial scaffold and cellular polarity of neural progenitors during embryogenesis. We found that Yap/Taz are necessary to establish and maintain junctional integrity of cerebellar neuroepithelium as prominent junction proteins are not maintained at the apical junction in the absence of Yap/Taz. Our study identifies a novel function of Yap/Taz in cerebellar foliation and finds that they are required to establish the radial glia scaffold and junctional stability.

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