Fgf20, or Fibroblast growth factor 20, is a neurotrophic factor and a member of the FGF9 subfamily. Its receptors include FGFR4, FGFR3b, FGFR2b, and FGFRc splice forms. It is highly expressed in the adult brain and is expressed in various regions during embryonic development. Fgf20 is associated with multiple biological processes and human diseases [1].

Fgf20 knockout (KO) mouse models have shown a variety of phenotypes. For example, Fgf20 KO mice exhibit congenital deafness, lack of hair, small kidneys, and delayed mammary ductal outgrowth, indicating its role in inner ear, hair, kidney, and mammary gland development [1]. In the cochlea, FGF20-FGFR1 signaling through MAPK and PI3K controls sensory progenitor differentiation, as shown by experiments inhibiting pathways downstream of FGFR1 in cochlea explant cultures [2]. In spinal cord injury mouse models, recombinant human FGF20 was found to mitigate necroptosis, reduce neural functional deficits, and promote repair [3]. In a traumatic brain injury mouse model, FGF20 reduced neurofunctional deficits, brain edema, and neuroinflammation, protecting the blood-brain barrier integrity [5]. Fgf20 KO mice also show skeletal dysmorphology and mineralization defects, especially in the spine and fingers, indicating its role in skeletal development and bone homeostasis [7].

In conclusion, Fgf20 plays essential roles in multiple biological processes such as embryonic development, organogenesis, and neural repair. The study of Fgf20 using KO mouse models has provided insights into its functions in diseases like congenital deafness, Parkinson's disease, cancer, and inflammatory bowel disease, suggesting its potential as a therapeutic target in these disease areas [1,3,5,7].

References:

1. Van Greenen, Justine D, Hockman, Dorit. 2023. FGF20. In Differentiation; research in biological diversity, 139, 100737. doi:10.1016/j.diff.2023.10.005. https://pubmed.ncbi.nlm.nih.gov/38007375/

2. Su, Yutao, Yang, Lu M, Ornitz, David M. 2020. FGF20-FGFR1 signaling through MAPK and PI3K controls sensory progenitor differentiation in the organ of Corti. In Developmental dynamics : an official publication of the American Association of Anatomists, 250, 134-144. doi:10.1002/dvdy.231. https://pubmed.ncbi.nlm.nih.gov/32735383/

3. Cai, Xiong, Xie, Zhenwen, Zhao, Juan, Xu, Jiake, Zhu, Sipin. . FGF20 promotes spinal cord injury repair by inhibiting the formation of necrotic corpuscle P-MLKL/P-RIP1/P-RIP3 in neurons. In Journal of cellular and molecular medicine, 28, e70109. doi:10.1111/jcmm.70109. https://pubmed.ncbi.nlm.nih.gov/39676730/

4. Katoh, Masaru. 2018. Multi‑layered prevention and treatment of chronic inflammation, organ fibrosis and cancer associated with canonical WNT/β‑catenin signaling activation (Review). In International journal of molecular medicine, 42, 713-725. doi:10.3892/ijmm.2018.3689. https://pubmed.ncbi.nlm.nih.gov/29786110/

5. Chen, Jun, Wang, Xue, Hu, Jian, Lin, Li, Li, Xiaokun. 2021. FGF20 Protected Against BBB Disruption After Traumatic Brain Injury by Upregulating Junction Protein Expression and Inhibiting the Inflammatory Response. In Frontiers in pharmacology, 11, 590669. doi:10.3389/fphar.2020.590669. https://pubmed.ncbi.nlm.nih.gov/33568994/

6. Wang, Xiaoli, Sun, Xiaoxuan, Zhang, Xiaona, Li, Hong, Xie, Anmu. 2017. Quantitative assessment of the effect of FGF20 rs12720208 variant on the risk of Parkinson's disease: a meta-analysis. In Neurological research, 39, 374-380. doi:10.1080/01616412.2017.1286542. https://pubmed.ncbi.nlm.nih.gov/28191856/

7. Dlugosova, Sylvie, Spoutil, Frantisek, Madureira Trufen, Carlos Eduardo, Sedlacek, Radislav, Prochazka, Jan. 2024. Skeletal dysmorphology and mineralization defects in Fgf20 KO mice. In Frontiers in endocrinology, 15, 1286365. doi:10.3389/fendo.2024.1286365. https://pubmed.ncbi.nlm.nih.gov/39129916/