The history of the Wnt pathway is an adventure that takes us from mice and flies to frogs, zebrafish and beyond, sketching the outlines of a molecular signalling cascade along the way. Here, we specifically highlight the instrumental role that developmental biology has played throughout. We take the reader on a journey, starting with developmental genetics studies that identified some of the main molecular players, through developmental model organisms that helped unravel their biochemical function and cell biological activities. Culminating in complex analyses of stem cell fate and dynamic tissue growth, these efforts beautifully illustrate how different disciplines provided missing pieces of a puzzle. Together, they have shaped our mechanistic understanding of the Wnt pathway as a conserved signalling process in development and disease. Today, researchers are still uncovering additional roles for Wnts and other members of this multifaceted signal transduction pathway, opening up promising new avenues for clinical applications.

Funding

R.v.A.’s research is funded by KWF Kankerbestrijding (ANW 2013-6057, UVA 2015-8014, UVA 11082-2017) and an NWO VIDI grant from the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (864.13.002). K.E.W. is a Marie Skłodowska-Curie Actions Individual Fellowship fellow (European Union's Horizon 2020 research and innovation programme, 706443). R.N. is an investigator of the Howard Hughes Medical Institute and receives research funding from the California Institute of Regenerative Medicine.

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