PUBLICATION
Inhibition of Jagged-mediated Notch signaling disrupts zebrafish biliary development and generates multi-organ defects compatible with an Alagille syndrome phenocopy
- Authors
- Lorent, K., Yeo, S.Y., Oda, T., Chandrasekharappa, S., Chitnis, A., Matthews, R.P., and Pack, M.
- ID
- ZDB-PUB-041029-9
- 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
Citation
Lorent, K., Yeo, S.Y., Oda, T., Chandrasekharappa, S., Chitnis, A., Matthews, R.P., and Pack, M. (2004) Inhibition of Jagged-mediated Notch signaling disrupts zebrafish biliary development and generates multi-organ defects compatible with an Alagille syndrome phenocopy. Development (Cambridge, England). 131(22):5753-5766.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping