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Hepatocyte nuclear factor 4alpha orchestrates expression of cell adhesion proteins during the epithelial transformation of the developing liver. Proc Natl Acad Sci U S A 2006 May 30;103(22):8419-24

Date

05/23/2006

Pubmed ID

16714383

Pubmed Central ID

PMC1482507

DOI

10.1073/pnas.0600246103

Scopus ID

2-s2.0-33744795211   186 Citations

Abstract

Epithelial formation is a central facet of organogenesis that relies on intercellular junction assembly to create functionally distinct apical and basal cell surfaces. How this process is regulated during embryonic development remains obscure. Previous studies using conditional knockout mice have shown that loss of hepatocyte nuclear factor 4alpha (HNF4alpha) blocks the epithelial transformation of the fetal liver, suggesting that HNF4alpha is a central regulator of epithelial morphogenesis. Although HNF4alpha-null hepatocytes do not express E-cadherin (also called CDH1), we show here that E-cadherin is dispensable for liver development, implying that HNF4alpha regulates additional aspects of epithelial formation. Microarray and molecular analyses reveal that HNF4alpha regulates the developmental expression of a myriad of proteins required for cell junction assembly and adhesion. Our findings define a fundamental mechanism through which generation of tissue epithelia during development is coordinated with the onset of organ function.

Author List

Battle MA, Konopka G, Parviz F, Gaggl AL, Yang C, Sladek FM, Duncan SA

Author

Michele A. Battle PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Cadherins
Cell Adhesion Molecules
Cell Differentiation
Epithelial Cells
Female
Gene Expression Regulation, Developmental
Hepatocyte Nuclear Factor 4
Intercellular Junctions
Liver
Male
Mice
Mice, Transgenic
Microscopy, Electron, Transmission