Wnt4 is a growth factor involved in multiple developmental processes. It is crucial in the development of the female phenotype in the fetus, such as in the development of the female reproductive tract, and in the maintenance of müllerian and reproductive tissues [2,3,6,7]. Wnt4 also participates in pathways like the Wnt signalling pathway [1]. It plays a significant role in tissue homeostasis and is associated with various diseases including several cancers, uterine fibroids, endometriosis, and infertility [2].

In cardiac fibroblasts, TEAD1 promotes the fibroblast-to-myofibroblast transition through the Wnt signalling pathway by targeting Wnt4. Conditional TEAD1 knockout in CFs-and myofibroblasts-specific cells ameliorated TAC-induced cardiac remodeling, suggesting Wnt4's role in pathological cardiac remodeling [1]. In mice, Wnt4 inactivation has shown its involvement in multiple steps of female reproductive development, including Müllerian duct regression, inhibition of steroidogenesis, etc. [6]. Nr4a1 overexpression promoted BMSC osteogenesis by enhancing Wnt4 transcription, and Nr4a1 bound to the Wnt4 promoter to regulate its expression, indicating Wnt4's role in bone formation [4]. In endometriosis, Wnt4 treatment reduced granulosa cell apoptosis and promoted macrophage polarization, with granulosa cell M-CSF being the main mediator [5].

In conclusion, Wnt4 is essential for female reproductive development, bone formation, and tissue homeostasis. Its dysregulation is associated with various diseases. Gene knockout and conditional knockout mouse models have been valuable in revealing its role in pathological cardiac remodeling, female reproductive development, endometriosis, and bone formation, providing insights into disease mechanisms and potential therapeutic targets.