Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 35, Pages 14896-14901Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0906348106
Keywords
zebrafish; pancreas; islet; insulin; lineage
Categories
Funding
- Larry L. Hillblom Foundation
- Juvenile Diabetes Research Foundation
- National Institutes of Health [DK075032]
- Packard Foundation
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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.
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