Origin of the zebrafish endocrine and exocrine pancreas

Department of Organismal Biology and Anatomy, The University of Chicago, Chicago, Illinois 60615, USA.
Developmental Dynamics (Impact Factor: 2.38). 06/2007; 236(6):1558-69. DOI: 10.1002/dvdy.21168
Source: PubMed


Here, we report a detailed fate map of the zebrafish pancreas at the early gastrula stage of development (6 hours postfertilization; hpf). We show that, at this stage, both pancreas and liver progenitors are symmetrically localized in two broad domains relative to the dorsal organizer. We demonstrate that the dorsal and ventral pancreatic buds can derive from common progenitor pools at 6 hpf, but often derive from independent populations. Endocrine vs. exocrine pancreas show a similar pattern of progenitors, consistent with descriptions of the dorsal bud being strictly endocrine and the ventral bud primarily exocrine. In general, we find that endocrine/dorsal bud progenitors are located more dorsally than the exocrine pancreas/ventral bud progenitors. Later in gastrulation (10 hpf), pancreas progenitors have migrated to bilateral domains at the equator of the embryo. Our fate map will assist with design and interpretation of future experiments to understand early pancreas development.

Download full-text


Available from: Andrea Ward
  • Source
    • "The fish pancreas does not often prove to be a ready source of tissue for electron microscopic study. The main fish pancreas is both anatomically [5] and developmentally [6] similar to the mammalian pancreas, whereas major differences are apparent in other fish species. In adult zebrafish, the main pancreas contains several principal islets surrounded by exocrine tissue. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The present work shows that a detailed description of the ultrastructure of the secretory cells of the South American catfish Rhamdia quelen pancreatic islets is presented. Evidence is offered to support the contention that the α-granules consist of a central and an outer portion of different electron densities and solubilities, that the δ-cells are most probably morphologically altered but viable α-cells, and that the β-granules possibly possess a repeating substructure and may therefore represent an intracellular crystalline storage form of insulin.
    Full-text · Article · Jan 2015
  • Source
    • "Expression of Pdx1 is very dynamic in the developing pancreas and genetic analyses using conditional and hypomorphic Pdx1 mutant alleles in mouse have already indicated that Pdx1 is important in various specification and differentiation events [38-41]. In zebrafish, fate-mapping studies indicated that a spatial separation of the future pancreatic DB versus VB progenitors is already established shortly after gastrulation (10 hpf) [42,43]. Medium levels of pdx1 expression during early somitogenesis (10 to 15 hpf) correlate with VB fate specification [44]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Insulin-producing beta cells emerge during pancreas development in two sequential waves. Recently described later-forming beta cells in zebrafish show high similarity to second wave mammalian beta cells in developmental capacity. Loss-of-function studies in mouse and zebrafish demonstrated that the homeobox transcription factors Pdx1 and Hb9 are both critical for pancreas and beta cell development and discrete stage-specific requirements for these genes have been uncovered. Previously, exocrine and endocrine cell recovery was shown to follow loss of pdx1 in zebrafish, but the progenitor cells and molecular mechanisms responsible have not been clearly defined. In addition, interactions of pdx1 and hb9 in beta cell formation have not been addressed. To learn more about endocrine progenitor specification, we examined beta cell formation following morpholino-mediated depletion of pdx1 and hb9. We find that after early beta cell reduction, recovery occurs following loss of either pdx1 or hb9 function. Unexpectedly, simultaneous knockdown of both hb9 and pdx1 leads to virtually complete and persistent beta cell deficiency. We used a NeuroD:EGFP transgenic line to examine endocrine cell behavior in vivo and developed a novel live-imaging technique to document emergence and migration of late-forming endocrine precursors in real time. Our data show that Notch-responsive progenitors for late-arising endocrine cells are predominantly post mitotic and depend on pdx1. By contrast, early-arising endocrine cells are specified and differentiate independent of pdx1. The nearly complete beta cell deficiency after combined loss of hb9 and pdx1 suggests functional cooperation, which we clarify as distinct roles in early and late endocrine cell formation. A novel imaging approach permitted visualization of the emergence of late endocrine cells within developing embryos for the first time. We demonstrate a pdx1-dependent progenitor population essential for the formation of duct-associated, second wave endocrine cells. We further reveal an unexpectedly low mitotic activity in these progenitor cells, indicating that they are set aside early in development.
    Full-text · Article · Oct 2011 · BMC Biology
  • Source
    • "Understanding the mechanisms that regulate pancreatic development has been facilitated by studies in model organisms, including zebrafish (Danio rerio). The exocrine component of the zebrafish pancreas arises from endodermal progenitor cells that migrate from the gut tube, requiring the transcriptional activities of pancreatic and duodenal homeobox (Pdx1) and pancreas-specific transcription factor (Ptf1a) (Yee et al., 2001; Biemar et al., 2001; Lin et al., 2004; Zecchin et al., 2004; Yee et al., 2005; Ward et al., 2007). Signaling pathways, including wingless-type mouse mammary tumor virus integration site family members (Wnt), fibroblast growth factor (Fgf) and sonic hedgehog (Shh), are implicated in the induction and patterning of exocrine pancreatic tissues (Goessling et al., 2008; Manfroid et al., 2007; Dong et al., 2007; Chung and Stainier, 2008). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Genetic analysis of pancreatic development has provided new insights into the mechanisms underlying the formation of exocrine pancreatic neoplasia. Zebrafish sweetbread (swd) mutants develop hypoplastic acini and dysmorphic ducts in the exocrine pancreas, with impeded progression of cell division cycle and of epithelial growth. Positional cloning and allelic complementation have revealed that the swd mutations affect the transient receptor potential melastatin-subfamily member 7 (trpm7) gene, which encodes a divalent cation-permeable channel with kinase activity. Supplementary Mg(2+) partially rescued the exocrine pancreatic defects of the trpm7 mutants by improving cell-cycle progression and growth and repressing the suppressor of cytokine signaling 3a (socs3a) gene. The role of Socs3a in Trpm7-mediated signaling is supported by the findings that socs3a mRNA level is elevated in the trpm7 mutants, and antisense inhibition of socs3a expression improved their exocrine pancreatic growth. TRPM7 is generally overexpressed in human pancreatic adenocarcinoma. TRPM7-deficient cells are impaired in proliferation and arrested in the G0-G1 phases of the cell division cycle. Supplementary Mg(2+) rescued the proliferative defect of the TRPM7-deficient cells. Results of this study indicate that Trpm7 regulates exocrine pancreatic development via the Mg(2+)-sensitive Socs3a pathway, and suggest that aberrant TRPM7-mediated signaling contributes to pancreatic carcinogenesis.
    Full-text · Article · Mar 2011 · Disease Models and Mechanisms
Show more