Three decades of Wnts: a personal perspective on how a scientific field developed

Abstract

Wnt genes and components of Wnt signalling pathways have been implicated in a wide spectrum of important biological phenomena, ranging from early organismal development to cell behaviours to several diseases, especially cancers. Emergence of the field of Wnt signalling can be largely traced back to the discovery of the first mammalian Wnt gene in 1982. In this essay, we mark the thirtieth anniversary of that discovery by describing some of the critical scientific developments that led to the flowering of this field of research.

Figure 1

A working map of the mouse int1 locus as drawn by RN and used from 1982 to 1984, with the position of various cloned genomic restriction fragments. Red lines indicate the presence of int1 exons, mapped in 1984. Note the location of Probe C, a genomic fragment hybridizing with int1 mRNA in mouse mammary tumours. At the bottom, the position of MMTV proviruses mapped in different tumours, with the position of the provirus in tumour #18, the starting point of the cloning of the locus, indicated at the right hand end.

Figure 2

Wnt signalling components as known in 1995 and 2000.

Figure 3

Participants of the 1991 Wnt meeting at UCSF. From left: RN, Andrew McMahon, Arend Sidow, Vladimir Pecenka, John Mason, Lee Fradkin, HV, Henk Roelink, Jasprina Noordermeer, Supriya Shivakumar, Frank van Leeuwen, Cindy Harryman, Jean-Paul Vincent, Jackie Papkoff, two unidentified people, Tony Brown, a third unidentified person, Helen Kwan. Top row, from left: Karl Willert, Neil Parkin, and Jan Kitajewski.

Figure 4

Celebration of discovery of Frizzleds as Wnt receptors at the 1996 Wnt meeting at Stanford. From left: Jeremy Nathans, Matthew Scott, RN, and HV.