ZFIN ID: ZDB-PUB-041029-9
Inhibition of Jagged-mediated Notch signaling disrupts zebrafish biliary development and generates multi-organ defects compatible with an Alagille syndrome phenocopy
Lorent, K., Yeo, S.Y., Oda, T., Chandrasekharappa, S., Chitnis, A., Matthews, R.P., and Pack, M.
Date: 2004
Source: Development (Cambridge, England)   131(22): 5753-5766 (Journal)
Registered Authors: Chandrasekharappa, Settara, Chitnis, Ajay, Lorent, Kristin, Pack, Michael, Yeo, Sang-Yeob
Keywords: Zebrafish, Notch, Jagged, Alagille Syndrome, Bile Duct, Biliary Development
MeSH Terms:
  • Alagille Syndrome/embryology
  • Alagille Syndrome/metabolism*
  • Alagille Syndrome/pathology
  • Animals
  • Animals, Genetically Modified
  • Bile Ducts/embryology
  • Bile Ducts/metabolism
  • Biliary Tract/embryology*
  • Biliary Tract/metabolism*
  • Calcium-Binding Proteins/antagonists & inhibitors
  • Calcium-Binding Proteins/genetics
  • Calcium-Binding Proteins/metabolism*
  • Intercellular Signaling Peptides and Proteins
  • Ligands
  • Liver/anatomy & histology
  • Liver/cytology
  • Liver/embryology
  • Liver/metabolism
  • Mammals/anatomy & histology
  • Membrane Proteins/metabolism*
  • Microscopy, Electron, Transmission
  • Receptors, Notch
  • Signal Transduction*
  • Zebrafish/abnormalities
  • Zebrafish/embryology*
  • Zebrafish/metabolism
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 15509774 Full text @ Development
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.