Dact2, also known as Dapper homolog 2, is a member of the DACT gene family. It plays crucial roles in tissue development and injury. Dact2 can affect the Wnt/β -catenin and TGF -β signaling pathways by regulating the phosphorylation levels of target proteins, which is important for processes like fibrosis and cell-fate determination. Gene-knockout models, such as the zebrafish Dact2 knockout model, are valuable for exploring its functions [1,2].

In a zebrafish Dact2 knockout model, the absence of Dact2 enhanced the expression of genes related to tumor invasion, migration, and epithelial-mesenchymal transition (EMT), and led to hyperplasia of the gastrointestinal epithelium, fibrosis in the pancreas and liver, and increased proliferation of pancreatic and hepatic bile ducts [2]. In Dact2 knockout mice, the loss of Dact2 alleviated cisplatin-induced nephrotoxicity, possibly through the regulation of the Igf1-MAPK axis associated with Wnt/β-catenin signaling [3].

In conclusion, Dact2 is involved in multiple biological processes, especially those related to fibrosis, EMT, and cell-fate regulation through its effects on the Wnt/β-catenin and TGF -β signaling pathways. Gene-knockout models, including zebrafish and mouse models, have been instrumental in revealing Dact2's role in various disease-related conditions, such as fibrosis, cancer, and drug-induced nephrotoxicity.