PUBLICATION

Endoderm Jagged induces liver and pancreas duct lineage in zebrafish

Authors
Zhang, D., Gates, K.P., Barske, L., Wang, G., Lancman, J.J., Zeng, X.I., Groff, M., Wang, K., Parsons, M.J., Crump, J.G., Dong, P.D.S.
ID
ZDB-PUB-171005-6
Date
2017
Source
Nature communications   8: 769 (Journal)
Registered Authors
Barske, Lindsey, Crump, Gage DeKoeyer, Dong, P. Duc, Gates, Keith, Lancman, Joseph, Li, Zhuyun (June), Parsons, Michael, Wang, Guangliang (Johnny), Zeng, Sean, Zhang, Danhua
Keywords
none
MeSH Terms
  • Jagged-2 Protein/genetics*
  • Zebrafish
  • Calcium-Binding Proteins/genetics*
  • Alagille Syndrome/genetics
  • Animals
  • Gene Expression Regulation, Developmental*
  • Endoderm/cytology
  • Endoderm/metabolism*
  • Bile Ducts, Intrahepatic/embryology*
  • Pancreatic Ducts/embryology*
  • Cell Lineage
  • Zebrafish Proteins/genetics*
(all 12)
PubMed
28974684 Full text @ Nat. Commun.
Abstract
Liver duct paucity is characteristic of children born with Alagille Syndrome (ALGS), a disease associated with JAGGED1 mutations. Here, we report that zebrafish embryos with compound homozygous mutations in two Notch ligand genes, jagged1b (jag1b) and jagged2b (jag2b) exhibit a complete loss of canonical Notch activity and duct cells within the liver and exocrine pancreas, whereas hepatocyte and acinar pancreas development is not affected. Further, animal chimera studies demonstrate that wild-type endoderm cells within the liver and pancreas can rescue Notch activity and duct lineage specification in adjacent cells lacking jag1b and jag2b expression. We conclude that these two Notch ligands are directly and solely responsible for all duct lineage specification in these organs in zebrafish. Our study uncovers genes required for lineage specification of the intrahepatopancreatic duct cells, challenges the role of duct cells as progenitors, and suggests a genetic mechanism for ALGS ductal paucity.The hepatopancreatic duct cells connect liver hepatocytes and pancreatic acinar cells to the intestine, but the mechanism for their lineage specification is unclear. Here, the authors reveal that Notch ligands Jagged1b and Jagged2b induce duct cell lineage in the liver and pancreas of the zebrafish.
Genes / Markers
Figures
Figure Gallery (11 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
b1105
    Point Mutation
    gz15TgTransgenic Insertion
      hu3425
        Point Mutation
        jh1TgTransgenic Insertion
          jh63TgTransgenic Insertion
            nl1TgTransgenic Insertion
              s5
                Point Mutation
                s870TgTransgenic Insertion
                  s959TgTransgenic Insertion
                    um14TgTransgenic Insertion
                      1 - 10 of 10
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      Target Reagent Reagent Type
                      jag1bMO1-jag1bMRPHLNO
                      jag2bMO1-jag2bMRPHLNO
                      1 - 2 of 2
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                      Fish
                      Antibodies
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      CFPEFGCFP
                      CreEFGCre
                      DsRedEFGDsRed
                      EGFPEFGEGFP
                      GFPEFGGFP
                      mCherryEFGmCherry
                      1 - 6 of 6
                      Show
                      Mapping
                      No data available