Wnt3 is a crucial signaling molecule that belongs to the WNT family. It plays a vital role in multiple biological processes, such as neural patterning, brain development, and stem-cell maintenance [4,5]. Wnt3 transduces signals through the WNT-β-catenin pathway, JNK pathway, or Ca2 +-releasing pathway via WNT receptors [1].

In zebrafish, Wnt3 spreads extracellularly, interacts with heparan sulfate proteoglycans (HSPG), and its binding to the receptor Frizzled1 (Fzd1) requires the co-receptor low-density lipoprotein receptor-related protein 5 (Lrp5), regulating brain development [4]. In mouse intestinal crypts, Paneth cells express Wnt3, which is an essential signal for the maintenance of Lgr5 stem cells. Genetic removal of Paneth cells leads to the loss of Lgr5 stem cells, indicating the importance of Wnt3 in stem-cell niche maintenance [5]. In adult mouse dorsal root ganglion (DRG) neurons, downregulation or overexpression of Wnt3 respectively enhances or inhibits axon regeneration ability, suggesting it is a key regulator of axon growth [6]. In cancer, Wnt3 promotes chemoresistance to 5-Fluorouracil in oral squamous cell carcinoma via activating the canonical β-catenin pathway, and in colorectal cancer, p53 promotes Wnt3 transcription, leading to cancer stem cell activation and tumor recurrence after 5-FU treatment [3,7]. Also, certain Wnt3 polymorphisms (rs3809857 and rs9890413) are associated with non-syndromic cleft lip with or without cleft palate [2].

In conclusion, Wnt3 is essential for various biological functions including neural development, stem-cell maintenance, and axon regeneration. In disease conditions, especially in cancer and non-syndromic cleft lip with or without cleft palate, Wnt3 has been shown to play significant roles. The use of animal models like zebrafish and mice has been crucial in uncovering these functions and disease associations, providing valuable insights into potential therapeutic targets.