On the role of lateral stabilization during early patterning in the pancreas

Research output: Contribution to journalResearch articleContributedpeer-review

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 languageEnglish
Article number20120766
JournalJournal of the Royal Society Interface
Volume10
Issue number79
Publication statusPublished - 2012
Peer-reviewedYes

External IDs

Scopus 84872260133
ORCID /0000-0003-0137-5106/work/142244228

Keywords

Keywords

  • lateral stabilization, pancreas