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

J R Soc Interface. 2013 Feb;10(79):20120766. doi: 10.1098/rsif.2012.0766.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acinar Cells / cytology
  • Animals
  • Cell Communication / physiology*
  • Cell Differentiation / physiology*
  • Gene Expression Regulation / physiology*
  • In Vitro Techniques
  • Islets of Langerhans / cytology
  • Mice
  • Models, Biological
  • Morphogenesis / physiology*
  • Multipotent Stem Cells / physiology*
  • Pancreas / cytology
  • Pancreas / embryology*
  • Receptors, Notch / metabolism
  • Signal Transduction / physiology

Substances

  • Receptors, Notch