One Wnt to lead them all: a Wnt1 primer

Differentiation. 2025 Jul-Aug;144:100884. doi: 10.1016/j.diff.2025.100884. Epub 2025 Jun 24.

ABSTRACT

Wnt1 was originally identified by virtue of its mutant phenotype in Drosophila and its causation of mammary tumors in mice, but, in its history, Wnt1 has been a nexus for ground-breaking discoveries in developmental biology, evolutionary biology, and disease. Wnt1 orthologs are found across the animal kingdom and play a role in a multitude of developmental and homeostatic mechanisms involving proliferation, cell fate specification, stem cell maintenance and tissue homeostasis. In vertebrates, Wnt1 is located in a syntenic chromosome neighborhood that is essential to its conserved expression in the developing nervous system. Wnt1 is essential for nervous system development, in particular for the midbrain and anterior hindbrain. Wnt1 also is essential for bone homeostasis, and mutant alleles are behind severe cases of recessive osteogenesis imperfecta in humans. This primer reviews the illustrious history of Wnt1, its gene structure and regulation, expression, loss-of-function consequences, and connection to human disease.

PMID:40580644 | DOI:10.1016/j.diff.2025.100884