title: On the role of lateral stabilization during early patterning in the pancreas.
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.
authors.affiliation: Center for Information Services and High Performance Computing, Technische Universität Dresden, Dresden, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: de Back
authors.forename: Joseph Xu
authors.initials: JX
authors.lastname: Zhou
authors.forename: Lutz
authors.initials: L
authors.lastname: Brusch
mesh_terms: D061354:Acinar Cells / Q000166:cytology; D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000166:cytology; D051379:Mice; D008954:Models, Biological; D009024:Morphogenesis / Q000502:physiology*; D039902:Multipotent Stem Cells / Q000502:physiology*; D010179:Pancreas / Q000166:cytology / Q000196:embryology*; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D051880:Receptors, Notch