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).
Documents
33171:637151
PDF
dev202098.pdf - Published Version
Available under License Creative Commons Attribution.
dev202098.pdf - Published Version
Available under License Creative Commons Attribution.
Download (6MB) | Preview
33171:637152
PDF
dev202098supp.pdf - Supplemental Material
Available under License Creative Commons Attribution.
dev202098supp.pdf - Supplemental Material
Available under License Creative Commons Attribution.
Download (3MB) | Preview
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.
More Information
Statistics
Downloads
Downloads per month over past year
Downloads per month over past year for
"dev202098.pdf"
Downloads per month over past year for
"dev202098supp.pdf"
Metrics
Altmetric Badge
Dimensions Badge
Share
Actions (login required)
![]() |
View Item |