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

Fay Cooper (Lead / Corresponding author), Celine Souilhol, Scott Haston, Shona Gray, Katy Boswell, Antigoni Gogolou, Thomas J. R. Frith, Dylan Stavish, Bethany M. James, Daniel Bose, Jacqueline Kim Dale, Anestis Tsakiridis (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
4 Downloads (Pure)

Abstract

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.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalDevelopment
Volume151
Issue number3
Early online date12 Feb 2024
DOIs
Publication statusPublished - Feb 2024

Keywords

  • Axial progenitors
  • HOX
  • Neuromesodermal progenitors (NMPs)
  • Notch signalling
  • Human
  • Neuromesodermal progenitors
  • NMPs
  • Chick

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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