Aldh1-expressing endocrine progenitor cells regulate secondary islet formation in larval zebrafish pancreas

PLoS One. 2013 Sep 17;8(9):e74350. doi: 10.1371/journal.pone.0074350. eCollection 2013.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Dehydrogenase 1 Family
  • 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*

Substances

  • Biomarkers
  • Isoenzymes
  • Receptors, Notch
  • Aldehyde Dehydrogenase 1 Family
  • ALDH1A1 protein, mouse
  • Retinal Dehydrogenase