Document Detail


A classification of ductal plate malformations based on distinct pathogenic mechanisms of biliary dysmorphogenesis.
MedLine Citation:
PMID:  21391226     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Ductal plate malformations (DPM) are developmental anomalies considered to result from lack of ductal plate remodeling during bile duct morphogenesis. In mice, bile duct development is initiated by the formation of primitive ductal structures lined by two cell types, namely ductal plate cells and hepatoblasts. During ductal plate remodeling the primitive ductal structures mature to ducts as a result from differentiation of the ductal plate cells and hepatoblasts to cholangiocytes. We here report that this process is conserved in human fetal liver. These findings prompted us to evaluate how DPM develop in three mouse models, namely mice with livers deficient in Hepatocyte Nuclear Factor (HNF)6, HNF1β or cystin-1 (cpk mice). Human liver from a patient with a HNF1B/TCF2 mutation, and from fetuses affected with Autosomal Recessive Polycystic Kidney Disease (ARPKD) were also analysed. Despite the epistatic relationship between HNF6, HNF1β and cystin-1, the three mouse models displayed distinct morphogenic mechanisms of DPM. They all developed biliary cysts lined by cells with abnormal apico-basal polarity. However, the absence of HNF6 led to an early defect in ductal plate cell differentiation. In HNF1β-deficient liver, maturation of the primitive ductal structures was impaired. Cpk mouse livers and human fetal ARPKD showed normal differentiation and maturation but abnormal duct expansion. CONCLUSION: DPM is the common end-point of distinct defects initiated at distinct stages of bile duct morphogenesis. Our observations provide a new pathogenic classification of DPM. (HEPATOLOGY 2011.).
Authors:
Peggy Raynaud; Joshua Tate; Céline Callens; Sabine Cordi; Patrick Vandersmissen; Rodolphe Carpentier; Christine Sempoux; Olivier Devuyst; Christophe E Pierreux; Pierre Courtoy; Karin Dahan; Katty Delbecque; Sébastien Lepreux; Marco Pontoglio; Lisa M Guay-Woodford; Frédéric P Lemaigre
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-9
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  -     ISSN:  1527-3350     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 American Association for the Study of Liver Diseases.
Affiliation:
Université catholique de Louvain, de Duve Institute, Brussels, Belgium.
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