On the role of lateral stabilization during early patterning in the pancreas
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
The cell fate decision of multi-potent pancreatic progenitor cells between the exocrine and endocrine lineages is regulated by Notch signalling, mediated by cell–cell interactions. However, canonical models of Notch-mediated lateral inhibition cannot explain the scattered spatial distribution of endocrine cells and the cell-type ratio in the developing pancreas. Based on evidence from acinar-to-islet cell transdifferentiation in vitro, we propose that lateral stabilization, i.e. positive feedback between adjacent progenitor cells, acts in parallel with lateral inhibition to regulate pattern formation in the pancreas. A simple mathematical model of transcriptional regulation and cell–cell interaction reveals the existence of multi-stability of spatial patterns whose simultaneous occurrence causes scattering of endocrine cells in the presence of noise. The scattering pattern allows for control of the endocrine-to-exocrine cell-type ratio by modulation of lateral stabilization strength. These theoretical results suggest a previously unrecognized role for lateral stabilization in lineage specification, spatial patterning and cell-type ratio control in organ development.
Details
Original language | English |
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Article number | 20120766 |
Journal | Journal of the Royal Society Interface |
Volume | 10 |
Issue number | 79 |
Publication status | Published - 2012 |
Peer-reviewed | Yes |
External IDs
Scopus | 84872260133 |
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ORCID | /0000-0003-0137-5106/work/142244228 |
Keywords
Keywords
- lateral stabilization, pancreas