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Context-dependent TGFβ family signalling in cell fate regulation

Nature Reviews Molecular Cell Biology volume 24, pages 876–894 (2023)Cite this article

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Abstract

The transforming growth factor-β (TGFβ) family are a large group of evolutionarily conserved cytokines whose signalling modulates cell fate decision-making across varying cellular contexts at different stages of life. Here we discuss new findings in early embryos that reveal how, in contrast to our original understanding of morphogen interpretation, robust cell fate specification can originate from a noisy combination of signalling inputs and a broad range of signalling levels. We compare this evidence with novel findings on the roles of TGFβ family signalling in tissue maintenance and homeostasis during juvenile and adult life, spanning the skeletal, haemopoietic and immune systems. From these comparisons, it emerges that in contrast to robust developing systems, relatively small perturbations in TGFβ family signalling have detrimental effects at later stages in life, leading to aberrant cell fate specification and disease, for example in cancer or congenital disorders. Finally, we highlight novel strategies to target and amend dysfunction in signalling and discuss how gleaning knowledge from different fields of biology can help in the development of therapeutics for aberrant TGFβ family signalling in disease.

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Fig. 1: TGFβ family signalling.
Fig. 2: Nodal and BMP signalling in germ-layer patterning.
Fig. 3: TGFβ signalling in tissue homeostasis.
Fig. 4: TGFβ function on cancer and stromal cell fate in tumours.

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Acknowledgements

The authors thank T. Evan and Ł. Wieteska for helpful comments on the manuscript. Work in the Hill laboratory is supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (CC2021), the UK Medical Research Council (CC2021) and the Wellcome Trust (CC2021), and by the Engineering and Physical Sciences Research Council (EPSRC) (EP/V038028/1).

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  1. Luca Guglielmi

    Present address: Division of Cell Biology, MRC Laboratory of Molecular Biology, Cambridge, UK

  2. These authors contributed equally: Louise Richardson, Scott G. Wilcockson.

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  1. Developmental Signalling Laboratory, The Francis Crick Institute, London, UK

    Louise Richardson, Scott G. Wilcockson, Luca Guglielmi & Caroline S. Hill

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  1. Louise Richardson
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The authors contributed equally to all aspects of the article.

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Correspondence to Caroline S. Hill.

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Richardson, L., Wilcockson, S.G., Guglielmi, L. et al. Context-dependent TGFβ family signalling in cell fate regulation. Nat Rev Mol Cell Biol 24, 876–894 (2023). https://doi.org/10.1038/s41580-023-00638-3

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