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miR-285– Yki/Mask double-negative feedback loop mediates blood–brain barrier integrity in Drosophila

作者:Dong Li, Yanling Liu, Chunli Pei, Peng Zhang, Linqing Pan, Jing Xiao, Songshu Meng, Zengqiang Yuan, Xiaolin Bi · 发表于:Proceedings of the National Academy of Sciences · 年份:2017 · DOI:10.1073/pnas.1613233114 · 被引用次数:33 · 研究领域:Hippo pathway signaling and YAP/TAZ、Wnt/β-catenin signaling in development and cancer、RNA Research and Splicing

Significance The blood–brain barrier (BBB) is evolutionarily conserved from invertebrates to vertebrates to ensure a well-balanced ionic environment for proper neuronal functions. The Hippo pathway is a highly conserved signaling pathway essential for organ size control and tissue homeostasis. Until now, whether Hippo pathway is required for BBB maintenance has been unknown. We show here that miR-285 is an upstream regulator of the Hippo pathway, which can directly target Yorkie (Yki) cofactor Multiple Ankyrin repeats Single KH domain (Mask). miR-285 and Yki/Mask form a double-negative feedback loop to finely tune endoreplication of subperineurial glial (SPG) cells to keep proper cell size and maintain a functional BBB. Our findings propose an exquisite microRNA-mediated regulatory circuit that regulates Hippo signaling activity and tissue homeostasis during development.