Polycystic liver disease: ductal plate malformation and the primary cilium

ES Wills, R Roepman, JPH Drenth - Trends in molecular medicine, 2014 - cell.com
ES Wills, R Roepman, JPH Drenth
Trends in molecular medicine, 2014cell.com
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 …
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.
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