Document Detail


Liver progenitor cells fold up a cell monolayer into a double-layered structure during tubular morphogenesis.
MedLine Citation:
PMID:  19297530     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Naoki Tanimizu; Atsushi Miyajima; Keith E Mostov
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-03-18
Journal Detail:
Title:  Molecular biology of the cell     Volume:  20     ISSN:  1939-4586     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-01     Completed Date:  2009-07-20     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2486-94     Citation Subset:  IM    
Affiliation:
Departments of Anatomy, and Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA 94143-2140, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Bile Ducts / cytology,  enzymology,  growth & development*
Cell Culture Techniques / methods*
Cell Line
Cell Movement
Cell Proliferation
Genes, Dominant
Hepatocyte Nuclear Factor 1 / metabolism
Liver / cytology*,  enzymology,  growth & development
Mice
Models, Biological
Morphogenesis*
Phosphatidylinositol 3-Kinases / metabolism
Proto-Oncogene Proteins c-akt / metabolism
Stem Cells / cytology*,  enzymology
Chemical
Reg. No./Substance:
126548-29-6/Hepatocyte Nuclear Factor 1; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  The exocyst protein sec10 is necessary for primary ciliogenesis and cystogenesis in vitro.
Next Document:  Focal adhesion kinase modulates cell adhesion strengthening via integrin activation.