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: 2.67). 06/2007; 236(6):1558-69. DOI: 10.1002/dvdy.21168
Source: PubMed

ABSTRACT 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.

1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In a forward genetic screen for regulators of pancreas development in zebrafish, we identified donut(s908) , a mutant which exhibits failed outgrowth of the exocrine pancreas. The s908 mutation leads to a leucine to arginine substitution in the ectodomain of the hepatocyte growth factor (HGF) tyrosine kinase receptor, Met. This missense mutation impedes the proteolytic maturation of the receptor, its trafficking to the plasma membrane, and diminishes the phospho-activation of its kinase domain. Interestingly, during pancreatogenesis, met and its hgf ligands are expressed in pancreatic epithelia and mesenchyme, respectively. Although Met signaling elicits mitogenic and migratory responses in varied contexts, normal proliferation rates in donut mutant pancreata together with dysmorphic, mislocalized ductal cells suggest that met primarily functions motogenically in pancreatic tail formation. Treatment with PI3K and STAT3 inhibitors, but not with MAPK inhibitors, phenocopies the donut pancreatic defect, further indicating that Met signals through migratory pathways during pancreas development. Chimera analyses showed that Met-deficient cells were excluded from the duct, but not acinar, compartment in the pancreatic tail. Conversely, wild-type intrapancreatic duct and "tip cells" at the leading edge of the growing pancreas rescued the donut phenotype. Altogether, these results reveal a novel and essential role for HGF signaling in the intrapancreatic ducts during exocrine morphogenesis.
    PLoS Genetics 07/2013; 9(7):e1003650. DOI:10.1371/journal.pgen.1003650 · 8.17 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Progenitors of the zebrafish pronephros, red blood and trunk endothelium all originate from the ventral mesoderm and often share lineage with one another, suggesting that their initial patterning is linked. Previous studies have shown that spadetail (spt) mutant embryos, defective in tbx16 gene function, fail to produce red blood cells, but retain the normal number of endothelial and pronephric cells. We report here that spt mutants are deficient in all the types of early blood, have fewer endothelial cells as well as far more pronephric cells compared to wildtype. In vivo cell tracing experiments reveal that blood and endothelium originate in spt mutants almost exclusively from the dorsal mesoderm whereas, pronephros and tail originate from both dorsal and ventral mesoderm. Together these findings suggest possible defects in posterior patterning. In accord with this, gene expression analysis show that mesodermal derivatives within the trunk and tail of spt mutants have acquired more posterior identity. Secreted signaling molecules belonging to the Fgf, Wnt and Bmp families have been implicated as patterning factors of the posterior mesoderm. Further investigation demonstrate that Fgf and Wnt signaling are elevated throughout the nonaxial region of the spt gastrula. By manipulating Fgf signaling we show that Fgfs both promote pronephric fate and repress blood and endothelial fate. We conclude that Tbx16 plays an important role in regulating the balance of intermediate mesoderm fates by attenuating Fgf activity.
    Developmental Biology 09/2013; 383(1). DOI:10.1016/j.ydbio.2013.08.018 · 3.64 Impact Factor
  • Acta Hydrobiologica Sinica 07/2009; 33(4):702-708. DOI:10.3724/SP.J.1035.2009.40702

Full-text (2 Sources)

Available from
May 31, 2014