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
  • Gene Expression Regulation, Developmental
  • Animals
  • Molecular Probe Techniques
  • Integrases/analysis*
  • Integrases/genetics
  • Integrases/metabolism
  • Cell Proliferation*
  • Insulin-Secreting Cells/cytology*
  • Insulin-Secreting Cells/metabolism*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Interphase*
  • Cell Differentiation
  • Insulin/metabolism
  • Genes, Reporter*
(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)
Show all Figures
Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
jh1TgTransgenic Insertion
    m567
      		Point Mutation
      m1018TgTransgenic Insertion
        s854TgTransgenic Insertion
          s892TgTransgenic Insertion
            s923TgTransgenic Insertion
              s924TgTransgenic Insertion
                zf5TgTransgenic Insertion
                  1 - 8 of 8
                  Show
                  Human Disease / Model
                  No data available
                  Sequence Targeting Reagents
                  Target Reagent Reagent Type
                  prkciMO2-prkciMRPHLNO
                  1 - 1 of 1
                  Show
                  Fish
                  Fish
                  jh1Tg
                  m1018Tg
                  prkcim567/m567
                  s854Tg
                  s892Tg
                  s923Tg
                  s924Tg
                  zf5Tg
                  1 - 8 of 8
                  Show
                  Antibodies
                  Name Type Antigen Genes Isotypes Host Organism
                  Ab1-gcgmonoclonal
                    		IgG1Mouse
                    Ab2-inspolyclonalGuinea pig
                    Ab2-islmonoclonalIgG2bMouse
                    ab2-sstpolyclonal
                      		IgGRabbit
                      1 - 4 of 4
                      Show
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      CeruleanEFGCerulean
                      CFPEFGCFP
                      CreEFGCre
                      DsRedEFGDsRed
                      EGFPEFGEGFP
                      GFPEFGGFP
                      mCherryEFGmCherry
                      NTREFGNTR
                      VenusEFGVenus
                      1 - 9 of 9
                      Show
                      Mapping
                      No data available
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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.