Notch signaling regulates bile duct morphogenesis in mice

Alagille syndrome is a developmental disorder caused predominantly by mutations in the Jagged1 (JAG1) gene, which encodes a ligand for Notch family receptors. A characteristic feature of Alagille syndrome is intrahepatic bile duct paucity. We described previously that mice doubly heterozygous for Ja...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2008-03, Vol.3 (3), p.e1851-e1851
Main Authors: Lozier, Julie, McCright, Brent, Gridley, Thomas
Format: Article
Language:English
Subjects:
Alagille syndrome
Analysis
Animals
Bile
Bile ducts
Bile Ducts - growth & development
Biliary tract
Cell cycle
Cell fate
Clonal deletion
Defects
Developmental Biology
Developmental Biology/Cell Differentiation
Developmental Biology/Embryology
Developmental Biology/Morphogenesis and Cell Biology
Developmental disabilities
Embryonic development
Embryos
Gallbladder diseases
Gastroenterology and Hepatology/Biliary Tract
Gene deletion
Genes
Genetic aspects
Heterozygote
Homeostasis
Immunohistochemistry
Jagged1 protein
Laboratories
Liver
Medical research
Mice
Morphogenesis
Mutation
Notch2 protein
Receptors
Receptors, Notch - genetics
Receptors, Notch - metabolism
Rodents
Signal Transduction
Transcription factors
Veins & arteries
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Alagille syndrome is a developmental disorder caused predominantly by mutations in the Jagged1 (JAG1) gene, which encodes a ligand for Notch family receptors. A characteristic feature of Alagille syndrome is intrahepatic bile duct paucity. We described previously that mice doubly heterozygous for Jag1 and Notch2 mutations are an excellent model for Alagille syndrome. However, our previous study did not establish whether bile duct paucity in Jag1/Notch2 double heterozygous mice resulted from impaired differentiation of bile duct precursor cells, or from defects in bile duct morphogenesis. Here we characterize embryonic biliary tract formation in our previously described Jag1/Notch2 double heterozygous Alagille syndrome model, and describe another mouse model of bile duct paucity resulting from liver-specific deletion of the Notch2 gene. Our data support a model in which bile duct paucity in Notch pathway loss of function mutant mice results from defects in bile duct morphogenesis rather than cell fate specification.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0001851