Wnt Signaling Pathway - Discovery

Discovery

The first Wnt gene was discovered by Roeland Nusse and Harold Varmus in 1982 when they observed activation of Int1 (integration 1) in the breast tumors of mice infected with mouse mammary tumor virus (MMTV), in which Int was identified as a vertebrate gene near several integration sites of MMTV. The name Wnt is a portmanteau of Int and Wg (wingless) in Drosophila, which is the best characterized Wnt gene. Although the wingless gene was originally identified as a recessive mutation affecting wing and haltere development in Drosophila melanogaster, wingless has been important towards understanding the Wnt signaling system in other organisms. Its function as a segment polarity gene was discovered by Christiane Nüsslein-Volhard and Eric Wieschaus in Drosophila with mutations in the Wg signaling pathway, for which they won the Nobel Prize in Physiology or Medicine in 1995. It was not until 1987 that researchers found that Wg was the homologue to mammalian Int1 due to a common evolutionary origin evinced by similar amino acid sequences of their encoded proteins.

Mutations of the wingless gene in the fruit fly were found in wingless flies, while tumors caused by MMTV were found to have copies of the virus integrated into the genome forcing overproduction of one of several Wnt genes. The ensuing effort to understand how similar genes produce such different effects has revealed that Wnt proteins are a major class of secreted morphogenic ligands of profound importance in establishing the pattern of development in the bodies of all multicellular organisms studied.