Fgf6, a member of the fibroblast growth factor family, has been proposed to have important functions in myogenesis [1,5,7]. It is involved in various signaling pathways such as the PI3K/AKT, MAPK, Hippo, and calcineurin-dependent pathways, and is crucial for muscle-related biological processes and potentially for metabolism regulation [1,2,3,6,7,8]. Genetic models, like knockout (KO) mouse models, have been valuable in studying its functions.

Analysis of Fgf6 (-/-) mutant mice has provided insights into its role in myogenesis. In the regenerating soleus of Fgf6 (-/-) mice, myotube appearance was accelerated, along with increased expression of differentiation and structural markers, and changes in myofiber types, indicating a dose-dependent effect of Fgf6 in muscle regeneration, with high doses stimulating myogenic stem cell proliferation and lower doses regulating muscle differentiation and phenotype via a calcineurin-signaling pathway [7]. Knockdown of Fgf6 synthesis in a myocardial infarction mouse model led to poorer heart function, while treatment with recombinant human Fgf6 protein improved heart function, reduced infarct size, and promoted cardiac repair by inhibiting the Hippo pathway [2]. In oral squamous cell carcinoma, Fgf6 was weakly expressed and may inhibit the disease process by regulating the PI3K-AKT/MAPK pathway [3]. In bladder cancer, silencing of Fgf6 hampered aerobic glycolysis and angiogenesis by regulating the PI3K/Akt and MAPK signaling pathways [6].

In conclusion, Fgf6 plays a vital role in muscle-related processes including myogenesis, muscle regeneration, and potentially in the regulation of whole-body metabolism as seen in protecting mice from diet-induced obesity and insulin resistance [1,4,7,8]. Its functions in disease conditions such as myocardial infarction, oral squamous cell carcinoma, and bladder cancer are also significant, with gene knockout mouse models being instrumental in revealing these roles, providing potential targets for disease treatment and prevention.