PUBLICATION

Distinct populations of quiescent and proliferative pancreatic β-cells identified by HOTcre mediated labeling

Authors
Hesselson, D., Anderson, R.M., Beinat, M., and Stainier, D.Y.
ID
ZDB-PUB-090828-26
Date
2009
Source
Proceedings of the National Academy of Sciences of the United States of America   106(35): 14896-14901 (Journal)
Registered Authors
Anderson, Ryan, Hesselson, Daniel, Stainier, Didier
Keywords
zebrafish, pancreas, islet, insulin, lineage
MeSH Terms
  • Molecular Probe Techniques
  • Insulin/metabolism
  • Cell Proliferation*
  • Animals
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Genes, Reporter*
  • Integrases/analysis*
  • Integrases/genetics
  • Integrases/metabolism
  • Gene Expression Regulation, Developmental
  • Cell Differentiation
  • Interphase*
  • Insulin-Secreting Cells/cytology*
  • Insulin-Secreting Cells/metabolism*
(all 16)
PubMed
19706417 Full text @ Proc. Natl. Acad. Sci. USA
Abstract
Pancreatic beta-cells are critical regulators of glucose homeostasis, and they vary dramatically in their glucose stimulated metabolic response and levels of insulin secretion. It is unclear whether these parameters are influenced by the developmental origin of individual beta-cells. Using HOTcre, a Cre-based genetic switch that uses heat-induction to precisely control the temporal expression of transgenes, we labeled two populations of beta-cells within the developing zebrafish pancreas. These populations originate in distinct pancreatic buds and exhibit gene expression profiles suggesting distinct functions during development. We find that the dorsal bud derived beta-cells are quiescent and exhibit a marked decrease in insulin expression postembryonically. In contrast, ventral bud derived beta-cells proliferate actively, and maintain high levels of insulin expression compared with dorsal bud derived beta-cells. Therapeutic strategies to regulate beta-cell proliferation and function are required to cure pathological states that result from excessive beta-cell proliferation (e.g., insulinoma) or insufficient beta-cell mass (e.g., diabetes mellitus). Our data reveal the existence of distinct populations of beta-cells in vivo and should help develop better strategies to regulate beta-cell differentiation and proliferation.
Genes / Markers
Figures
Figure Gallery (6 images)
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
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Citation
Hesselson, D., Anderson, R.M., Beinat, M., and Stainier, D.Y. (2009) Distinct populations of quiescent and proliferative pancreatic β-cells identified by HOTcre mediated labeling. Proceedings of the National Academy of Sciences of the United States of America. 106(35):14896-14901.