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The origin and evolution of Wnt signalling

Nature Reviews Genetics (2024)Cite this article

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Abstract

The Wnt signal transduction pathway has essential roles in the formation of the primary body axis during development, cellular differentiation and tissue homeostasis. This animal-specific pathway has been studied extensively in contexts ranging from developmental biology to medicine for more than 40 years. Despite its physiological importance, an understanding of the evolutionary origin and primary function of Wnt signalling has begun to emerge only recently. Recent studies on very basal metazoan species have shown high levels of conservation of components of both canonical and non-canonical Wnt signalling pathways. Furthermore, some pathway proteins have been described also in non-animal species, suggesting that recruitment and functional adaptation of these factors has occurred in metazoans. In this Review, we summarize the current state of research regarding the evolutionary origin of Wnt signalling, its ancestral function and the characteristics of the primal Wnt ligand, with emphasis on the importance of genomic studies in various pre-metazoan and basal metazoan species.

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Fig. 1: Wnt signalling pathways.
Fig. 2: Overview of components of Wnt secretion, trafficking and inhibition pathways in pre-metazoans and metazoans.
Fig. 3: Overview of the components of the canonical and non-canonical Wnt signalling pathways in pre-metazoans and metazoans.
Fig. 4: The evolutionary origin of Wnt signalling.

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Acknowledgements

Research in the groups of M.B. and T.W.H. is supported by the Deutsche Forschungsgemeinschaft Collaborative Research Center CRC/SFB1324 Projects A01 and A05 (project number 331351713) on Mechanisms and Functions of Wnt signalling. The authors thank the Wnt CRC Consortium for the numerous stimulating discussions and exchanges.

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Authors and Affiliations

  1. Division of Signalling and Functional Genomics, German Cancer Research Centre (DKFZ), Heidelberg, Germany

    Michaela Holzem & Michael Boutros

  2. Department of Cell and Molecular Biology & BioQuant, Heidelberg University, Heidelberg, Germany

    Michaela Holzem & Michael Boutros

  3. Faculty of Medicine Mannheim, Heidelberg University, Heidelberg, Germany

    Michaela Holzem & Michael Boutros

  4. Institute for Human Genetics, Medical Faculty Heidelberg, Heidelberg University, Heidelberg, Germany

    Michaela Holzem & Michael Boutros

  5. Centre for Organismal Studies (COS), Heidelberg University, Heidelberg, Germany

    Thomas W. Holstein

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  1. Michaela Holzem
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M.H. researched the literature and wrote the article. All authors provided substantial contributions to the discussions of the content and reviewed and/or edited the manuscript.

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Holzem, M., Boutros, M. & Holstein, T.W. The origin and evolution of Wnt signalling. Nat Rev Genet (2024). https://doi.org/10.1038/s41576-024-00699-w

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