Molecular mechanisms regulating epithelial morphogenesis during the development of bile ducts

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We revealed that α1-containing laminin regulated the lineage determination of cholangiocytes and the initial stage of bile duct morphogenesis, whereas α5-containing laminin contributes to the formation of mature duct structures. We also searched genes upregulated in mature cholangiocytes and identified a transcription factor grainyhead like 2(Grhl2). We introduced Grhl2 into HPPL, a liver progenitor cell line, and found that Grhl2 enlarged the central lumen of cysts. We further found that Grhl2 enhanced barrier function of the monolayer of HPPL and upregulated expression of Claudin3, Claudin4, and Rab25. Thus, we conclude that Grhl2 promotes the maturation of epithelial lumen by governing the molecular network among Clandin3, Claudin4, and Rab253.