Pygo1, a homolog of Drosophila Pygo, is a core interaction factor in the Wnt/β -catenin signaling pathway. This pathway is crucial in various biological processes, including development and disease. Genetic models, such as mouse models, are valuable for studying Pygo1's functions [1,2,3,4].

In a cardiac-specific overexpression mouse model, Pygo1 led to pathological cardiac hypertrophy, accompanied by declined cardiac function. The canonical β -catenin/TCF4 complex was abundant, and downstream Wnt signaling genes were upregulated. Inhibition of β -catenin rescued the phenotype, and in vivo down-regulation of Pygo1 antagonized agonist-induced cardiac hypertrophy, indicating its role in pathological cardiac hypertrophy via the Wnt/β -catenin pathway [1]. In lung cancer cells, overexpression of Pygo1 enhanced cell proliferation, invasion, and migration through the Wnt/β -catenin pathway [2]. In human umbilical cord mesenchymal stromal/stem cells, overexpression of PYGO1 promoted differentiation into early cardiac lineage cells, regulated by the canonical Wnt/β -catenin signaling [3]. Pygo1 homozygous mutant mice were viable and fertile with no detectable developmental defects, while Pygo1/Pygo2 double homozygous mutants showed disturbed ureteric bud and metanephric mesenchyme-derived compartments in kidney development, suggesting Pygo1 and Pygo2 function as quantitative transducers of Wnt signal intensity [4].

In conclusion, Pygo1 plays a significant role in the Wnt/β -catenin signaling pathway, influencing biological processes like cardiac development and disease, as well as cancer cell behavior. Mouse models, especially gene knockout and overexpression models, have been instrumental in revealing these functions, providing insights into potential therapeutic targets for cardiac diseases and cancer [1,2,3,4].