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Peer-reviewedCC BY 4.0Development (Cambridge, England)

Notch signalling governs human enteric nervous system progenitor dynamics

  • Antigoni Gogolou1,2
  • Nikolas Stefanidis1,3
  • Fay Cooper1,2
  • Guillaume Blin4,5
  • Stanley E. Strawbridge1,6,7
  • Alexander G. Fletcher2,3,7
  • Anestis Tsakiridis1,2
7 affiliations
  1. 1Centre for Stem Cell Biology, School of Biosciences, The University of Sheffield, Sheffield S10 2TN, UK
  2. 2Neuroscience Institute, The University of Sheffield, Sheffield S10 2TN, UK
  3. 3School of Mathematical and Physical Sciences, University of Sheffield, Hicks Building, Hounsfield Road, Sheffield S3 7RH, UK
  4. 4Institute for Stem Cell Research, School of Biological Sciences, The University of Edinburgh, Edinburgh EH16 4UU, UK
  5. 5Centre for Regenerative Medicine, Institute for Regeneration and Repair, The University of Edinburgh, Edinburgh EH16 4UU, UK
  6. 6Bateson Centre for Disease Mechanisms, University of Sheffield, Sheffield, UK
  7. 7Insigneo Institute, University of Sheffield, Sheffield S10 2TA, UK
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Abstract

The enteric nervous system (ENS) is the main branch of the peripheral nervous system that innervates the gastrointestinal tract controlling vital functions. It arises during embryogenesis via migration, proliferation and differentiation of neural crest-derived ENS progenitors. Perturbation of these processes, caused by mutations in key signalling pathway components and transcription factors, prevents progenitor colonisation of the distal gut, causing aganglionic phenotypes and enteric neuropathies such as Hirschsprung (HSCR) disease. While animal models implicate Notch signalling in ENS specification, its role in human ENS progenitor cell fate decisions remains unclear. Here, we employ a human pluripotent stem cell-based model to show that Notch signalling is a key regulator of human ENS progenitor dynamics. Quantitative modelling of our in vitro data indicates that Notch inhibition accelerates progenitor differentiation without substantially altering neuronal versus glial lineage bias. Furthermore, we establish that Notch signalling controls human ENS progenitor migration by influencing migration velocity and directionality. Together, these findings provide mechanistic insights into how Notch signalling disruption may contribute to the pathogenesis of human intestinal aganglionosis.

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Cite

BibTeXRIS
BibTeX
@article{gogolou2026notch,
  title = {{Notch signalling governs human enteric nervous system progenitor dynamics}},
  author = {Antigoni Gogolou and Nikolas Stefanidis and Fay Cooper and Guillaume Blin and Stanley E. Strawbridge and Alexander G. Fletcher and Anestis Tsakiridis},
  journal = {Development (Cambridge, England)},
  year = {2026},
  month = oct,
  doi = {10.1242/dev.205775},
  url = {https://doi.org/10.1242/dev.205775},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Notch signalling governs human enteric nervous system progenitor dynamics
AU  - Antigoni Gogolou
AU  - Nikolas Stefanidis
AU  - Fay Cooper
AU  - Guillaume Blin
AU  - Stanley E. Strawbridge
AU  - Alexander G. Fletcher
AU  - Anestis Tsakiridis
PY  - 2026
DA  - 2026/10/23
JO  - Development (Cambridge, England)
DO  - 10.1242/dev.205775
UR  - https://doi.org/10.1242/dev.205775
AB  - The enteric nervous system (ENS) is the main branch of the peripheral nervous system that innervates the gastrointestinal tract controlling vital functions. It arises during embryogenesis via migration, proliferation and differentiation of neural crest-derived ENS progenitors. Perturbation of these processes, caused by mutations in key signalling pathway components and transcription factors, prevents progenitor colonisation of the distal gut, causing aganglionic phenotypes and enteric neuropathies such as Hirschsprung (HSCR) disease. While animal models implicate Notch signalling in ENS specification, its role in human ENS progenitor cell fate decisions remains unclear. Here, we employ a human pluripotent stem cell-based model to show that Notch signalling is a key regulator of human ENS progenitor dynamics. Quantitative modelling of our in vitro data indicates that Notch inhibition accelerates progenitor differentiation without substantially altering neuronal versus glial lineage bias. Furthermore, we establish that Notch signalling controls human ENS progenitor migration by influencing migration velocity and directionality. Together, these findings provide mechanistic insights into how Notch signalling disruption may contribute to the pathogenesis of human intestinal aganglionosis.
SN  - 0950-1991
SN  - 1477-9129
ER  -