PUBLICATION
Retinoids signal directly to zebrafish endoderm to specify insulin-expressing {beta}-cells
- Authors
- Stafford, D., White, R.J., Kinkel, M.D., Linville, A., Schilling, T.F., and Prince, V.E.
- ID
- ZDB-PUB-060207-10
- Date
- 2006
- Source
- Development (Cambridge, England) 133(5): 949-956 (Journal)
- Registered Authors
- Kinkel, Mary, Prince, Victoria E., Schilling, Tom, Stafford, David
- Keywords
- Pancreas, Zebrafish, Insulin, ß-Cell, Endoderm
- MeSH Terms
-
- High Mobility Group Proteins/metabolism
- Zebrafish Proteins/metabolism
- Zebrafish/embryology*
- Zebrafish/metabolism
- Pancreas, Exocrine/cytology
- Pancreas, Exocrine/embryology
- Pancreas, Exocrine/metabolism
- Signal Transduction
- Insulin-Secreting Cells/cytology*
- Insulin-Secreting Cells/metabolism
- Mesoderm/cytology
- Mesoderm/metabolism
- Retinoids/metabolism*
- Transcription Factors/metabolism
- Receptors, Retinoic Acid/genetics
- Receptors, Retinoic Acid/physiology
- SOX Transcription Factors
- Endoderm/cytology*
- Endoderm/metabolism
- Cell Differentiation*
- Animals
- Pancreas/cytology
- Pancreas/embryology*
- Pancreas/metabolism
- PubMed
- 16452093 Full text @ Development
Citation
Stafford, D., White, R.J., Kinkel, M.D., Linville, A., Schilling, T.F., and Prince, V.E. (2006) Retinoids signal directly to zebrafish endoderm to specify insulin-expressing {beta}-cells. Development (Cambridge, England). 133(5):949-956.
Abstract
During vertebrate development, the endodermal germ layer becomes regionalized along its anteroposterior axis to give rise to a variety of organs, including the pancreas. Genetic studies in zebrafish and mice have established that the signaling molecule retinoic acid (RA) plays a crucial role in endoderm patterning and promotes pancreas development. To identify how RA signals to pancreatic progenitors in the endoderm, we have developed a novel cell transplantation technique, using the ability of the SOX32 transcription factor to confer endodermal identity, to selectively target reagents to (or exclude them from) the endodermal germ layer of the zebrafish. We show that RA synthesized in the anterior paraxial mesoderm adjacent to the foregut is necessary for the development of insulin-expressing beta-cells. Conversely, RA receptor function is required in the foregut endoderm for insulin expression, but not in mesoderm or ectoderm. We further show that activation of RA signal transduction in endoderm alone is sufficient to induce insulin expression. Our results reveal that RA is an instructive signal from the mesoderm that directly induces precursors of the endocrine pancreas. These findings suggest that RA will have important applications in the quest to induce islets from stem cells for therapeutic uses.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping