Nuclear Isoform of FGF13 Regulates Postnatal Neurogenesis in Hippocampus Through Epigenetic Mechanism

The hippocampus is one of the two niches in mammalian brain with persistent neurogenesis into adulthood. The neurogenic capability of hippocampal neural stem cells (NSCs) declines with age but the molecular mechanisms of this process remain unknown. In this study, we found that fibroblast growth factors 13 (FGF13) is essential for the postnatal neurogenesis in mouse hippocampus and FGF13 deficiency impairs learning and memory. In particular, we found that the nuclear isoform of FGF13, FGF13A, is involved in the maintenance of NSCs and the suppression of neuron differentiation during postnatal hippocampal development. Furthermore, we found 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 suggested that FGF13A is an important regulator for maintaining the self-renewal and neurogenic capacity of NSCs in postnatal hippocampus, revealing a novel epigenetic function of FGFs in neurogenesis.