title: Polycystic liver disease: ductal plate malformation and the primary cilium.
abstract: Polycystic livers are found in autosomal dominant polycystic kidney disease (ADPKD), caused by polycystic kidney disease (PKD)1 and PKD2 mutations in virtually all cases, and in isolated polycystic liver disease (PCLD), where 20% of cases are caused by mutations in Protein kinase C substrate 80K-H (PRKCSH) or SEC63. Loss of heterozygosity in single hepatoblasts leads to underlying cystogenic ductal plate malformations. Crucially, actual components driving this development remain elusive. Recent advances have unraveled the roles of transforming growth factor (TGF)-β, Notch and Wnt signaling, transcriptional regulators such as hepatocyte nuclear factor (HNF)6 and HNF1β, as well as cilium function in hepatobiliary organogenesis. In polycystic liver disease, mutation or defective co-translational processing of key elements required for primary cilium formation have been implicated. This review recapitulates liver patterning factors in hepatobiliary development and extracts molecular players in hepatic cystogenesis.
authors: Department of Medicine, Division of Gastroenterology and Hepatology, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands; Department of Human Genetics, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands.
authors: Edgar S
authors: ES
authors: Wills
authors: Department of Human Genetics, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands; Radboud Institute of Molecular Life Sciences, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands.
authors: Ronald
authors: R
authors: Roepman
authors: Department of Medicine, Division of Gastroenterology and Hepatology, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands. Electronic address: JoostPHDrenth@CS.com.
authors: Joost P H
authors: JP
authors: Drenth
mesh_terms: D000818:Animals; D001653:Bile Ducts, Intrahepatic / Q000002:abnormalities* / Q000378:metabolism; D002923:Cilia / Q000235:genetics / Q000378:metabolism*; D003560:Cysts / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008107:Liver Diseases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D050396:TRPP Cation Channels / Q000235:genetics / Q000378:metabolism
chemical_list: D050396:TRPP Cation Channels
keywords: ductal plate malformation; hepatic cystogenesis; hepatobiliary organogenesis; loss of heterozygosity; polycystic liver disease; primary cilium