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

Pancreas, Exocrine/cytology
Pancreas, Exocrine/embryology
Pancreas, Exocrine/metabolism
High Mobility Group Proteins/metabolism
Zebrafish/embryology*
Zebrafish/metabolism
Endoderm/cytology*
Endoderm/metabolism
SOX Transcription Factors
Cell Differentiation*
Zebrafish Proteins/metabolism
Animals
Insulin-Secreting Cells/cytology*
Insulin-Secreting Cells/metabolism
Transcription Factors/metabolism
Retinoids/metabolism*
Signal Transduction
Receptors, Retinoic Acid/genetics
Receptors, Retinoic Acid/physiology
Mesoderm/cytology
Mesoderm/metabolism
Pancreas/cytology
Pancreas/embryology*
Pancreas/metabolism

(all 24)

PubMed

16452093 Full text @ Development

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

Figures