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Nf2-Yap signaling controls the expansion of DRG progenitors and glia during DRG development

机译:Nf2-Yap信号传导控制DRG发育过程中DRG祖细胞和神经胶质细胞的扩增

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摘要

Molecular mechanisms governing the maintenance and proliferation of dorsal root ganglia (DRG) progenitors are largely unknown. Here we reveal that the Hippo pathway regulates the expansion of DRG progenitors and glia during mammalian DRG development. The key effectors of this pathway, transcriptional coactivators Yap and Taz, are expressed in DRG progenitors and glia during DRG development but are at least partially inhibited from activating transcription. Aberrant YAP activation leads to overexpansion of DRG progenitor and glial populations. We further show that the Neurofibromatosis 2 (Nf2) tumor suppressor inhibits Yap during DRG development. Loss of Nf2 leads to similar phenotypes as does YAP hyperactivation, and deleting Yap suppresses these phenotypes. Our study demonstrates that Nf2-Yap signaling plays important roles in controlling the expansion of DRG progenitors and glia during DRG development.
机译:控制背根神经节(DRG)祖细胞维持和增殖的分子机制在很大程度上尚不清楚。在这里,我们揭示了河马通路在哺乳动物DRG发育过程中调节DRG祖细胞和神经胶质细胞的扩增。该途径的关键效应子,转录共激活因子Yap和Taz,在DRG发育过程中在DRG祖细胞和神经胶质细胞中表达,但至少部分被抑制激活转录。 YAP异常激活导致DRG祖细胞和神经胶质种群过度扩张。我们进一步表明,神经纤维瘤病2(Nf2)肿瘤抑制因子抑制DRG发育过程中的Yap。 Nf2的丢失会导致类似的表型,就像YAP过度激活一样,删除Yap会抑制这些表型。我们的研究表明,Nf2-Yap信号传导在DRG发育过程中控制DRG祖细胞和神经胶质细胞的扩张中起重要作用。

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