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On the role of lateral stabilization during early patterning in the pancreas.
- Source :
-
Journal of the Royal Society, Interface [J R Soc Interface] 2013 Feb; Vol. 10 (79), pp. 20120766. - Publication Year :
- 2013
-
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.
- Subjects :
- Acinar Cells cytology
Animals
In Vitro Techniques
Islets of Langerhans cytology
Mice
Models, Biological
Pancreas cytology
Receptors, Notch metabolism
Signal Transduction physiology
Cell Communication physiology
Cell Differentiation physiology
Gene Expression Regulation physiology
Morphogenesis physiology
Multipotent Stem Cells physiology
Pancreas embryology
Subjects
Details
- Language :
- English
- ISSN :
- 1742-5662
- Volume :
- 10
- Issue :
- 79
- Database :
- MEDLINE
- Journal :
- Journal of the Royal Society, Interface
- Publication Type :
- Academic Journal
- Accession number :
- 23193107
- Full Text :
- https://doi.org/10.1098/rsif.2012.0766