title: Characterization of Notch receptor expression in the developing mammalian heart and liver.
abstract: Alagille syndrome (AGS) is an autosomal dominant disorder characterized by bile duct paucity along with cardiovascular, skeletal, and ophthalmologic defects. The identification of JAG1 as the AGS disease gene revealed the crucial role of the Notch signaling pathway in the development of multiple organ systems in humans. Patients with identical mutations in JAG1 demonstrate extreme clinical variability, suggesting that other factors may influence the severity of the developmental defects in this disorder. We have defined the temporal and spatial expression patterns of the Notch receptor genes in the developing mammalian heart and liver in order to identify potential ligand/receptor interactions during embryogenesis. In the developing heart, both Notch1 and Notch2 are expressed in the outflow tracts and the epicardium, in specific cell populations previously shown to express JAG1. These cells are destined to undergo epithelial-to-mesenchymal transformation. In the newborn mouse liver, Notch2 and Notch3 are expressed in opposing cell populations, suggesting they play different roles in cell fate determination during bile duct development. JAG1 is also expressed in cells adjacent to those expressing Notch2, suggesting a possible ligand receptor relationship. The Notch receptors have distinct roles in cell fate determination in different organ systems.
authors.affiliation: Division of Gastroenterology, Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Loomes
authors.forename: Darren B
authors.initials: DB
authors.lastname: Taichman
authors.forename: Curtis L
authors.initials: CL
authors.lastname: Glover
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Williams
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Markowitz
authors.forename: David A
authors.initials: DA
authors.lastname: Piccoli
authors.forename: H Scott
authors.initials: HS
authors.lastname: Baldwin
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Oakey
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D002319:Cardiovascular System / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008099:Liver / Q000196:embryology / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D011506:Proteins; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins