Wnt1, a key activator of the Wnt-signaling cascade, is of great biological importance. It plays pivotal roles in bone metabolism, neural development, and other biological processes. In bone, it is involved in pathways like Hippo/YAP-signaling and bone morphogenetic protein (BMP) signaling; in neural development, it is crucial for midbrain dopaminergic neuron development and the development of structures in the central nervous system [1,2,3]. Genetic models, especially mouse models, have been instrumental in studying its functions.

In mouse models, inactivation of Wnt1 in osteoblasts causes severe osteoporosis and spontaneous bone fractures, while conditional Wnt1 expression in osteoblasts promotes rapid bone mass increase in developing, adult, and aged mice, indicating its key role in bone mass regulation [6]. In limb mesenchymal cells, deletion of Wnt1 leads to a severe ostepenic bone phenotype and early-onset spontaneous fractures [4]. In a Wnt1-inducible transgenic mouse model targeting specific cell types in the periodontium, Wnt1 was shown to be a strong promoter of cementum and alveolar bone formation, but over-expression for long periods was associated with periodontal breakdown and ectopic mineralization [5]. In a Wnt1 lack-of-function mouse model, the habenula showed an enlarged volume due to increased proliferation of its neuroblasts, and the fasciculus retroflexus had a wider, disorganized distribution and misrouted axons [3].

In conclusion, Wnt1 is a multi-functional gene. Its role in bone metabolism, as revealed through gene knockout (KO) and conditional knockout (CKO) mouse models, has significant implications for treating orthopedic complications like osteoporosis and fracture non-union. In neural development, it is essential for the proper formation and function of certain neuronal populations and tracts, which is relevant for understanding and potentially treating related neurological disorders.