Nuclear isoform of FGF13 regulates post-natal neurogenesis in the hippocampus through an epigenomic mechanism.

Cell Rep

Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; School of Future Technology, University of Chinese Academy of Sciences, Beijing 100049, China; Shanghai Center

Published: May 2021


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Article Abstract

The hippocampus is one of two niches in the mammalian brain with persistent neurogenesis into adulthood. The neurogenic capacity of hippocampal neural stem cells (NSCs) declines with age, but the molecular mechanisms of this process remain unknown. In this study, we find that fibroblast growth factor 13 (FGF13) is essential for the post-natal neurogenesis in mouse hippocampus, and FGF13 deficiency impairs learning and memory. In particular, we find that FGF13A, the nuclear isoform of FGF13, is involved in the maintenance of NSCs and the suppression of neuronal differentiation during post-natal hippocampal development. Furthermore, we find that FGF13A interacts with ARID1B, a unit of Brahma-associated factor chromatin remodeling complex, and suppresses the expression of neuron differentiation-associated genes through chromatin modification. Our results suggest that FGF13A is an important regulator for maintaining the self-renewal and neurogenic capacity of NSCs in post-natal hippocampus, revealing an epigenomic regulatory function of FGFs in neurogenesis.

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http://dx.doi.org/10.1016/j.celrep.2021.109127DOI Listing

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