Abstract
The Alagille Syndrome (AGS) is a heritable disorder affecting the liver and other organs. Causative dominant mutations in human Jagged 1 have been identified in most AGS patients. Related organ defects occur in mice that carry jagged 1 and notch 2 mutations. Multiple jagged and notch genes are expressed in the developing zebrafish liver. Compound jagged and notch gene knockdowns alter zebrafish biliary, kidney, pancreatic, cardiac and craniofacial development in a manner compatible with an AGS phenocopy. These data confirm an evolutionarily conserved role for Notch signaling in vertebrate liver development, and support the zebrafish as a model system for diseases of the human biliary system.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alagille Syndrome / embryology
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Alagille Syndrome / metabolism*
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Alagille Syndrome / pathology
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Animals
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Animals, Genetically Modified
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Bile Ducts / embryology
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Bile Ducts / metabolism
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Biliary Tract / embryology*
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Biliary Tract / metabolism*
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Calcium-Binding Proteins / antagonists & inhibitors
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Calcium-Binding Proteins / genetics
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Calcium-Binding Proteins / metabolism*
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Intercellular Signaling Peptides and Proteins
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Jagged-1 Protein
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Jagged-2 Protein
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Ligands
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Liver / anatomy & histology
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Liver / cytology
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Liver / embryology
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Liver / metabolism
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Mammals / anatomy & histology
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Membrane Proteins / metabolism*
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Microscopy, Electron, Transmission
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Receptors, Notch
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Serrate-Jagged Proteins
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Signal Transduction*
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Zebrafish / abnormalities
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Zebrafish / embryology*
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Zebrafish / metabolism
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Zebrafish Proteins / antagonists & inhibitors
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Zebrafish Proteins / genetics
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Zebrafish Proteins / metabolism*
Substances
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Calcium-Binding Proteins
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Intercellular Signaling Peptides and Proteins
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JAG1 protein, human
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Jag1 protein, mouse
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Jag3 protein, zebrafish
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Jagged-1 Protein
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Jagged-2 Protein
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Ligands
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Membrane Proteins
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Receptors, Notch
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Serrate-Jagged Proteins
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Zebrafish Proteins
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jag1a protein, zebrafish
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jag2b protein, zebrafish