RNA-binding protein FXR2 regulates adult hippocampal neurogenesis by reducing Noggin expression

RNA 结合蛋白 FXR2 通过降低 Noggin 表达来调节成年海马神经发生

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作者:Weixiang Guo, Li Zhang, Devin M Christopher, Zhao-Qian Teng, Sarah R Fausett, Changmei Liu, Olivia L George, John Klingensmith, Peng Jin, Xinyu Zhao

Abstract

In adult mammalian brains, neurogenesis persists in the subventricular zone of the lateral ventricles (SVZ) and the dentate gyrus (DG) of the hippocampus. Although evidence suggest that adult neurogenesis in these two regions is subjected to differential regulation, the underlying mechanism is unclear. Here, we show that the RNA-binding protein FXR2 specifically regulates DG neurogenesis by reducing the stability of Noggin mRNA. FXR2 deficiency leads to increased Noggin expression and subsequently reduced BMP signaling, which results in increased proliferation and altered fate specification of neural stem/progenitor cells in DG. In contrast, Noggin is not regulated by FXR2 in the SVZ, because Noggin expression is restricted to the ependymal cells of the lateral ventricles, where FXR2 is not expressed. Differential regulation of SVZ and DG stem cells by FXR2 may be a key component of the mechanism that governs the different neurogenic processes in these two adult germinal zones.

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