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Modeling coexistence of oscillation and Delta/Notch-mediated lateral inhibition in pancreas development and neurogenesis.
J. Theor. Biol. 430, 32-44 (2017)
Publ. Version/Full Text
Research data
DOI
PMC
During pancreas development, Neurog3 positive endocrine progenitors are specified by Delta/Notch (D/N) mediated lateral inhibition in the growing ducts. During neurogenesis, genes that determine the transition from the proneural state to neuronal or glial lineages are oscillating before their expression is sustained. Although the basic gene regulatory network is very similar, cycling gene expression in pancreatic development was not investigated yet, and previous simulations of lateral inhibition in pancreas development excluded by design the possibility of oscillations. To explore this possibility, we developed a dynamic model of a growing duct that results in an oscillatory phase before the determination of endocrine progenitors by lateral inhibition. The basic network (D/N + Hes1 + Neurog3) shows scattered, stable Neurog3 expression after displaying transient expression. Furthermore, we included the Hes1 negative feedback as previously discussed in neurogenesis and show the consequences for Neurog3 expression in pancreatic duct development. Interestingly, a weakened HES1 action on the Hes1 promoter allows the coexistence of stable patterning and oscillations. In conclusion, cycling gene expression and lateral inhibition are not mutually exclusive. In this way, we argue for a unified mode of D/N mediated lateral inhibition in neurogenic and pancreatic progenitor specification.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Neurog3 ; Pancreatogenesis ; Cycling Gene Expression ; Endocrine Progenitor ; Simulation; Progenitor Cells; Endocrine Progenitors; Islet Differentiation; Gene-expression; Notch; Organogenesis; Mouse; Morphogenesis; Lineage; Growth
ISSN (print) / ISBN
0022-5193
e-ISSN
1095-8541
Journal
Journal of Theoretical Biology
Quellenangaben
Volume: 430,
Pages: 32-44
Publisher
Elsevier
Publishing Place
London
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Experimental Genetics (IEG)