title: Hepatic jagged1 expression studies.
abstract: Mutations in Jagged1, a Notch ligand, have been shown to result in Alagille syndrome (AGS), however, the causal link between haploinsufficiency of Jagged1 and intrahepatic ductal paucity is unknown. This survey was performed to determine the expression pattern of Jagged1 in the fetal and postnatal liver. Reverse transcription polymerase chain reaction (RT-PCR) showed Jagged1 expression in all samples studied including rat liver embryonic days 16 to 21, 1-day-old, 1-week-old, and 2-month-old adult rats. RT-PCR detected Jagged1 in total liver RNA extracted from cadaver organ donor samples from reduced human grafts and explanted native livers from a variety of pediatric disorders including AGS, biliary atresia, congenital hepatic fibrosis, sclerosing cholangitis, cystic fibrosis, fulminant hepatic failure, tyrosinemia, and chronic rejection. Immunohistochemistry showed Jagged1 expression in human fetal samples localized to the ductal plate from 14-week gestation onward. Expression in the postnatal liver was seen in biliary epithelium and zone 3 hepatocytes. In conclusion, these studies show that Jagged1 is expressed in the fetal and postnatal liver in health and disease. We show localization of expression by immunohistochemistry to ductal plate epithelium in human fetal samples and to the biliary epithelium and zone 3 hepatocytes in human postnatal samples. Our results show the localization of Jagged1 in fetal liver and demonstration of Jagged1 expression in postnatal rat and human liver specimens. Further studies of Jagged1 and the Notch signaling pathway are expected to elucidate mechanisms of the regulation of biliary epithelial growth and development.
authors.affiliation: Division of Gastroenterology and Nutrition, The Children's Hospital of Philadelphia, The University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: A A
authors.initials: AA
authors.lastname: Louis
authors.forename: P
authors.initials: P
authors.lastname: Van Eyken
authors.forename: B A
authors.initials: BA
authors.lastname: Haber
authors.forename: C
authors.initials: C
authors.lastname: Hicks
authors.forename: G
authors.initials: G
authors.lastname: Weinmaster
authors.forename: R
authors.initials: R
authors.lastname: Taub
authors.forename: E B
authors.initials: EB
authors.lastname: Rand
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D002135:Calcium-Binding Proteins; D002648:Child; D005314:Embryonic and Fetal Development / Q000502:physiology*; D005333:Fetus; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008099:Liver / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D008107:Liver Diseases / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins; D011506:Proteins / Q000235:genetics*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072099:Serrate-Jagged Proteins
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C000606275:Jag1 protein, rat; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D011506:Proteins; D000072099:Serrate-Jagged Proteins