Aldh1-expressing endocrine progenitor cells regulate secondary islet formation in larval zebrafish pancreas
- Authors
- Matsuda, H., Parsons, M.J., and Leach, S.D.
- ID
- ZDB-PUB-131119-45
- Date
- 2013
- Source
- PLoS One 8(9): e74350 (Journal)
- Registered Authors
- Leach, Steven D., Matsuda, Hiroki, 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.