Liver progenitor cells fold up a cell monolayer into a double-layered structure during tubular morphogenesis.

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 Cell

authors

Tanimizu N,Miyajima A,Mostov KE

doi

10.1091/mbc.e08-02-0177

subject

Has Abstract

pub_date

2009-05-01 00:00:00

pages

2486-94

issue

9

eissn

1059-1524

issn

1939-4586

pii

E08-02-0177

journal_volume

20

pub_type

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