Role of β-catenin in development of bile ducts

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• 作者：Sabine Cordi^a ; Cé ; cile Godard^b ; Thoueiba Saandi^a ; Patrick Jacquemin^a ; Satdarshan P. Monga^c ; Sabine Colnot^b ; Fré ; dé ; ric P. Lemaigre^a ; ^{frederic.lemaigre@uclouvain.be" class="auth_mail" title="E-mail the corresponding author}
• 关键词：APC ; adenomatous polyposis coli ; CK19 ; cytokeratin 19 ; E ; embryonic day ; HNF ; Hepatocyte Nuclear Factor ; OPN ; Osteopontin ; Muc1 ; Mucin-1 ; P ; postnatal day ; Sox9 ; SRY-related HMG box transcription factor 9 ; ZO1 ; Zonula Occludens-1
• 刊名：Differentiation
• 出版年：2016
• 出版时间：January-March 2016
• 年：2016
• 卷：91
• 期：1-3
• 页码：42-49
• 全文大小：9168 K

文摘

Beta-catenin is known to play stage- and cell-specific functions during liver development. However, its role in development of bile ducts has not yet been addressed. Here we used stage-specific in vivo gain- and loss-of-function approaches, as well as lineage tracing experiments in the mouse, to first demonstrate that β-catenin is dispensable for differentiation of liver precursor cells (hepatoblasts) to cholangiocyte precursors. Second, when β-catenin was depleted in the latter, maturation of cholangiocytes, bile duct morphogenesis and differentiation of periportal hepatocytes from cholangiocyte precursors was normal. In contrast, stabilization of β-catenin in cholangiocyte precursors perturbed duct development and cholangiocyte differentiation. We conclude that β-catenin is dispensable for biliary development but that its activity must be kept within tight limits. Our work is expected to significantly impact on in vitro differentiation of stem cells to cholangiocytes for toxicology studies and disease modeling.