ZFIN ID: ZDB-PUB-060207-10
Retinoids signal directly to zebrafish endoderm to specify insulin-expressing {beta}-cells
Stafford, D., White, R.J., Kinkel, M.D., Linville, A., Schilling, T.F., and Prince, V.E.
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:
  • Animals
  • Cell Differentiation*
  • Endoderm/cytology*
  • Endoderm/metabolism
  • High Mobility Group Proteins/metabolism
  • Insulin-Secreting Cells/cytology*
  • Insulin-Secreting Cells/metabolism
  • Mesoderm/cytology
  • Mesoderm/metabolism
  • Pancreas/cytology
  • Pancreas/embryology*
  • Pancreas/metabolism
  • Pancreas, Exocrine/cytology
  • Pancreas, Exocrine/embryology
  • Pancreas, Exocrine/metabolism
  • Receptors, Retinoic Acid/genetics
  • Receptors, Retinoic Acid/physiology
  • Retinoids/metabolism*
  • SOX Transcription Factors
  • Signal Transduction
  • Transcription Factors/metabolism
  • Zebrafish/embryology*
  • Zebrafish/metabolism
  • Zebrafish Proteins/metabolism
PubMed: 16452093 Full text @ Development
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.