Notch signalling influences cell fate decisions and HOX gene induction in axial progenitors

COOPER, Fay, SOUILHOL, Celine, HASTON, Scott, GRAY, Shona, BOSWELL, Katy, GOGOLOU, Antigoni, FRITH, Thomas J. R., STAVISH, Dylan, JAMES, Bethany M., BOSE, Daniel, KIM DALE, Jacqueline and TSAKIRIDIS, Anestis (2024). Notch signalling influences cell fate decisions and HOX gene induction in axial progenitors. Development, 151 (3).

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The generation of the post-cranial embryonic body relies on the coordinated production of spinal cord neurectoderm and presomitic mesoderm cells from neuromesodermal progenitors (NMPs). This process is orchestrated by pro-neural and pro-mesodermal transcription factors that are co-expressed in NMPs together with Hox genes, which are essential for axial allocation of NMP derivatives. NMPs reside in a posterior growth region, which is marked by the expression of Wnt, FGF and Notch signalling components. Although the importance of Wnt and FGF in influencing the induction and differentiation of NMPs is well established, the precise role of Notch remains unclear. Here, we show that the Wnt/FGF-driven induction of NMPs from human embryonic stem cells (hESCs) relies on Notch signalling. Using hESC-derived NMPs and chick embryo grafting, we demonstrate that Notch directs a pro-mesodermal character at the expense of neural fate. We show that Notch also contributes to activation of HOX gene expression in human NMPs, partly in a non-cell-autonomous manner. Finally, we provide evidence that Notch exerts its effects via the establishment of a negative-feedback loop with FGF signalling.

Item Type: Article
Additional Information: ** Article version: VoR ** From The Company of Biologists via Jisc Publications Router ** Licence for VoR version of this article: ** Peer reviewed: TRUE ** Acknowledgements: We thank Prof. Ivana Barbaric (University of Sheffield) for providing the H2B-RFP expression vector. We are grateful to Matt French, Sally Lowell, Matt Towers, Val Wilson and Sarah Bray for feedback/critical reading of the manuscript. **Journal IDs: pissn 0950-1991; eissn 1477-9129 **Article IDs: publisher-id: dev202098 **History: published_online 12-02-2024; published 01-02-2024; accepted 20-12-2023; submitted 16-06-2023 **License for this article: open-access,
Uncontrolled Keywords: Neuromesodermal progenitors, Chick, Human, HOX, NMPs, Notch signalling, Axial progenitors
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SWORD Depositor: Colin Knott
Depositing User: Colin Knott
Date Deposited: 15 Feb 2024 15:11
Last Modified: 15 Feb 2024 15:15

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