title: Aldh1-expressing endocrine progenitor cells regulate secondary islet formation in larval zebrafish pancreas.
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.
authors.affiliation: Department of Surgery and the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Matsuda
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Parsons
authors.forename: Steven D
authors.initials: SD
authors.lastname: Leach
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D004789:Enzyme Activation; D004848:Epithelium / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D007515:Islets of Langerhans / Q000201:enzymology / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D010179:Pancreas / Q000196:embryology / Q000378:metabolism*; D010183:Pancreatic Ducts / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D050697:Retinal Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology / Q000235:genetics*
chemical_list: D015415:Biomarkers; D007527:Isoenzymes; D051880:Receptors, Notch; D000080924:Aldehyde Dehydrogenase 1 Family; C515028:ALDH1A1 protein, mouse; D050697:Retinal Dehydrogenase