ZFIN ID: ZDB-PUB-131119-45
Aldh1-expressing endocrine progenitor cells regulate secondary islet formation in larval zebrafish pancreas
Matsuda, H., Parsons, M.J., and Leach, S.D.
Date: 2013
Source: PLoS One   8(9): e74350 (Journal)
Registered Authors: Leach, Steven D., Parsons, Michael
Keywords: none
MeSH Terms:
  • Animals
  • Biomarkers/metabolism
  • Cell Differentiation
  • Cell Proliferation
  • Enzyme Activation
  • Epithelium/metabolism
  • Gene Expression Regulation, Developmental*
  • Gene Expression Regulation, Enzymologic*
  • Islets of Langerhans/enzymology
  • Islets of Langerhans/metabolism*
  • Isoenzymes/genetics*
  • Isoenzymes/metabolism
  • Pancreas/embryology
  • Pancreas/metabolism*
  • Pancreatic Ducts/metabolism
  • Receptors, Notch/metabolism
  • Retinal Dehydrogenase/genetics*
  • Retinal Dehydrogenase/metabolism
  • Stem Cells/cytology
  • Stem Cells/metabolism*
  • Zebrafish/embryology
  • Zebrafish/genetics*
PubMed: 24147152 Full text @ PLoS One

Aldh1 expression is known to mark candidate progenitor populations in adult and embryonic mouse pancreas, and Aldh1 enzymatic activity has been identified as a potent regulator of pancreatic endocrine differentiation in zebrafish. However, the location and identity of Aldh1-expressing cells in zebrafish pancreas remain unknown. In this study we demonstrate that Aldh1-expressing cells are located immediately adjacent to 2F11-positive pancreatic ductal epithelial cells, and that their abundance dramatically increases during zebrafish secondary islet formation. These cells also express neurod, a marker of endocrine progenitor cells, but do not express markers of more mature endocrine cells such as pax6b or insulin. Using formal cre/lox-based lineage tracing, we further show that Aldh1-expressing pancreatic epithelial cells are the direct progeny of pancreatic notch-responsive progenitor cells, identifying them as a critical intermediate between multi-lineage progenitors and mature endocrine cells. Pharmacologic manipulation of Aldh1 enzymatic activity accelerates cell entry into the Aldh1-expressing endocrine progenitor pool, and also leads to the premature maturation of these cells, as evidenced by accelerated pax6b expression. Together, these findings suggest that Aldh1-expressing cells act as both participants and regulators of endocrine differentiation during zebrafish secondary islet formation.