Different levels of Notch signaling regulate quiescence, renewal and differentiation in pancreatic endocrine progenitors
- 1 May 2012
- journal article
- Published by The Company of Biologists in Development
- Vol. 139 (9), 1557-1567
- https://doi.org/10.1242/dev.076000
Abstract
Genetic studies have implicated Notch signaling in the maintenance of pancreatic progenitors. However, how Notch signaling regulates the quiescent, proliferative or differentiation behaviors of pancreatic progenitors at the single-cell level remains unclear. Here, using single-cell genetic analyses and a new transgenic system that allows dynamic assessment of Notch signaling, we address how discrete levels of Notch signaling regulate the behavior of endocrine progenitors in the zebrafish intrapancreatic duct. We find that these progenitors experience different levels of Notch signaling, which in turn regulate distinct cellular outcomes. High levels of Notch signaling induce quiescence, whereas lower levels promote progenitor amplification. The sustained downregulation of Notch signaling triggers a multistep process that includes cell cycle entry and progenitor amplification prior to endocrine differentiation. Importantly, progenitor amplification and differentiation can be uncoupled by modulating the duration and/or extent of Notch signaling downregulation, indicating that these processes are triggered by distinct levels of Notch signaling. These data show that different levels of Notch signaling drive distinct behaviors in a progenitor population.Keywords
This publication has 48 references indexed in Scilit:
- Ongoing Notch signaling maintains phenotypic fidelity in the adult exocrine pancreasDevelopmental Biology, 2012
- Notch Signaling Is Necessary to Maintain Quiescence in Adult Muscle Stem CellsThe International Journal of Cell Cloning, 2012
- Dose-dependent induction of distinct phenotypic responses to Notch pathway activation in mammary epithelial cellsProceedings of the National Academy of Sciences of the United States of America, 2010
- Notch-responsive cells initiate the secondary transition in larval zebrafish pancreasMechanisms of Development, 2009
- Presenilins, Notch dose control the fate of pancreatic endocrine progenitors during a narrow developmental windowGenes & Development, 2009
- Distinct populations of quiescent and proliferative pancreatic β-cells identified by HOTcre mediated labelingProceedings of the National Academy of Sciences of the United States of America, 2009
- Bmp inhibition is necessary for post-gastrulation patterning and morphogenesis of the zebrafish tailbudDevelopmental Biology, 2009
- NeuroD regulates proliferation of photoreceptor progenitors in the retina of the zebrafishMechanisms of Development, 2009
- Notch signaling is necessary for epithelial growth arrest by TGF-βThe Journal of cell biology, 2007
- Generation of Destabilized Green Fluorescent Protein as a Transcription ReporterJournal of Biological Chemistry, 1998