Abstract:
:Bile ducts are hepatic tubular structures that are lined by cholangiocytes, a type of liver epithelial cell. Cholangiocytes first form a single layer of cells, termed the ductal plate, surrounding the portal vein, which eventually remodels into the branching tubular network of bile ducts. The process of bile duct morphogenesis is not yet clear: a conventional model where cholangiocytes proliferate to duplicate a single layer of the ductal plate before lumen formation seems inconsistent with the observation that proliferation is dramatically reduced when hepatoblasts, liver progenitor cells, differentiate into cholangiocytes. Here, we developed a new culture system in which a liver progenitor cell line, HPPL, reorganizes from a monolayer to tubular structures in response to being overlaid with a gel containing type I collagen and Matrigel. We found that some of the HPPL in the monolayer depolarized and migrated to fold up the monolayer into a double-cell layer. These morphogenetic processes occurred without cell proliferation and required phosphatidylinositol 3-kinase and Akt activity. Later in morphogenesis, luminal space was generated between the two cell layers. This process, in particular enlargement of the apical lumen, involved transcriptional activity of HNF1beta. Thus, using this sandwich culture system, we could segregate tubulogenesis of bile ducts into distinct steps and found that the PI3K/Akt pathway and HNF1beta regulated different steps of the morphogenesis. Although the process of tubulogenesis in culture specifically resembled early bile duct formation, involvement of these two key players suggests that the sandwich culture might help us to find common principles of tubulogenesis in general.
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Tanimizu N,Miyajima A,Mostov KEdoi
10.1091/mbc.e08-02-0177subject
Has Abstractpub_date
2009-05-01 00:00:00pages
2486-94issue
9eissn
1059-1524issn
1939-4586pii
E08-02-0177journal_volume
20pub_type
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