FGF9 is required for Purkinje cell development and function in the cerebellum

Fibroblast growth factor 9 (FGF9) is a member of the fibroblast growth factor family, which is widely expressed in the central nervous system (CNS). It has been reported that deletion of FGF9 leads to defects in cerebellum development, including Purkinje cell defect. However, it is not clear how FGF9 regulating cerebellar development remains to be determined. Our results showed that in addition to disrupt Bergmann fiber scaffold formation and granule neuron migration, deletion of neuronal FGF9 led to ataxia defects. It affected development and function of Purkinje cells, and also changed the action potential threshold and excitation frequency. Mechanistically, depletion of FGF9 significantly changed neurotransmitter contents in Purkinje cells and led to preferential increase in inflammation, even downregulation in ERK signaling. Together, the data demonstrate that neuronal FGF9 is required for the development and function of Purkinje cells in the cerebellum. Insufficient FGF9 during cerebellum development will cause ataxia defects. [Display omitted] •FGF9 maintains mouse motor function via regulating Purkinje cell development•Ablation of FGF9 disrupts the intrinsic excitation of Purkinje cells•FGF9 deletion affects cerebellar neurotransmitter release•FGF9 deficiency leads to neuronal injury and inflammation in cerebellum Molecular biology; Neuroscience; Cell biology