Nuclear isoform of FGF13 regulates post-natal neurogenesis in the hippocampus through an epigenomic mechanism
Qiao-qiao Yang,
Ying-qi Zhai,
Hai-fang Wang,
Yu-chen Cai,
Xin-yue Ma,
Yan-qing Yin,
Yan-dong Li,
Guo-min Zhou,
Xu Zhang,
Gang Hu,
Jia-wei Zhou
Affiliations
Qiao-qiao Yang
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; Corresponding author
Ying-qi Zhai
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; Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu 210029, China
Hai-fang Wang
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
Yu-chen Cai
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
Xin-yue Ma
Department of Pharmacology, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China
Yan-qing Yin
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
Yan-dong Li
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
Guo-min Zhou
Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University, Shanghai 200032, China
Xu Zhang
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 for Brain Science and Brain-Inspired Intelligence Technology, Shanghai 201210, China
Gang Hu
Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu 210029, China; Department of Pharmacology, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China; Corresponding author
Jia-wei Zhou
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 for Brain Science and Brain-Inspired Intelligence Technology, Shanghai 201210, China; Co-innovation Center of Neuroregeneration, School of Medicine, Nantong University, Nantong, Jiangsu 226001, China; Corresponding author
Summary: 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.
