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Notch-responsive cells initiate the secondary transition in larval zebrafish pancreas |
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| Authors: | Michael J. Parsons Harshan Pisharath Shamila Yusuff John C. Moore Arndt F. Siekmann Nathan Lawson Steven D. Leach |
| Affiliation: | a Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA b McKusick-Nathans Institute for Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA c Department of Comparative Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA d Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605, USA e Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA |
| Abstract: | Zebrafish provide a highly versatile model in which to study vertebrate development. Many recent studies have elucidated early events in the organogenesis of the zebrafish pancreas; however, several aspects of early endocrine pancreas formation in the zebrafish are not homologous to the mammalian system. To better identify mechanisms of islet formation in the zebrafish, with true homology to those observed in mammals, we have temporally and spatially characterized zebrafish secondary islet formation. As is the case in the mouse, we show that Notch inhibition leads to precocious differentiation of endocrine tissues. Furthermore, we have used transgenic fish expressing fluorescent markers under the control of a Notch-responsive element to observe the precursors of these induced endocrine cells. These pancreatic Notch-responsive cells represent a novel population of putative progenitors that are associated with larval pancreatic ductal epithelium, suggesting functional homology between secondary islet formation in zebrafish and the secondary transition in mammals. We also show that Notch-responsive cells persist in the adult pancreas and possess the classical characteristics of centroacinar cells, a cell type believed to be a multipotent progenitor cell in adult mammalian pancreas. |
| Keywords: | Pancreatic progenitor Endocrine differentiation Zebrafish organogenesis Secondary transition Islet neogenesis |
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