Fgf22, a member of the FGF7 subfamily, functions as a paracrine factor. It is involved in various developmental processes, such as brain development, and is associated with pathways like those related to synapse formation and cellular differentiation. Genetic models, especially KO mouse models, have been crucial in studying its functions [4].

In zebrafish, fgf22 knockdown showed it was essential for ventral properties determination in the telencephalon and diencephalon, and for neurogenesis and gliogenesis in the forebrain, where it suppressed oligodendrocyte differentiation via the Fgf22-Fgfr2b axis without affecting cell proliferation [1]. In mouse models, FGF22 deletion led to hidden hearing loss due to impaired inner hair cell ribbon synapse function, with changes in related gene expressions like SNAP-25, Gipc3, and MEF2D [2]. Also, FGF22 over-expression in spinal cord injury mouse models enhanced neuronal rewiring and functional recovery [3].

In conclusion, Fgf22 plays essential roles in brain development, especially in neurogenesis and gliogenesis, as well as in the maintenance of inner hair cell ribbon synapses related to hearing function. Mouse KO models have revealed its significance in conditions like hidden hearing loss and spinal cord injury, providing insights into potential therapeutic targets for these diseases.

References:

1. Miyake, Ayumi, Ohmori, Takatoshi, Murakawa, Yuka. 2023. Fgf22 and Fgfr2b are required for neurogenesis and gliogenesis in the zebrafish forebrain. In Biochemical and biophysical research communications, 681, 212-217. doi:10.1016/j.bbrc.2023.09.070. https://pubmed.ncbi.nlm.nih.gov/37783119/

2. Hou, Shule, Zhang, Jifang, Wu, Yan, Yang, Jun, Li, Shuna. 2022. FGF22 deletion causes hidden hearing loss by affecting the function of inner hair cell ribbon synapses. In Frontiers in molecular neuroscience, 15, 922665. doi:10.3389/fnmol.2022.922665. https://pubmed.ncbi.nlm.nih.gov/35966010/

3. Aljović, Almir, Jacobi, Anne, Marcantoni, Maite, Kerschensteiner, Martin, Bareyre, Florence M. 2023. Synaptogenic gene therapy with FGF22 improves circuit plasticity and functional recovery following spinal cord injury. In EMBO molecular medicine, 15, e16111. doi:10.15252/emmm.202216111. https://pubmed.ncbi.nlm.nih.gov/36601738/

4. Furuta, Rise, Miyake, Ayumi. 2025. Fibroblast growth factor 22. In Differentiation; research in biological diversity, 143, 100860. doi:10.1016/j.diff.2025.100860. https://pubmed.ncbi.nlm.nih.gov/40139106/