Hepatocyte nuclear factor 4α orchestrates expression of cell adhesion proteins during the epithelial transformation of the developing liver

Michele A. Battle, Genevieve Konopka, Fereshteh Parviz, Alexandra Lerch Gaggl, Chuhu Yang, Frances M. Sladek, Stephen A. Duncan

Research output: Contribution to journalArticle

180 Scopus 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 4α (HNF4α) blocks the epithelial transformation of the fetal liver, suggesting that HNF4α is a central regulator of epithelial morphogenesis. Although HNF4α-null hepatocytes do not express E-cadherin (also called CDH1), we show here that E-cadherin is dispensable for liver development, implying that HNF4αa regulates additional aspects of epithelial formation. Microarray and molecular analyses reveal that HNF4α 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.

Original languageEnglish (US)
Pages (from-to)8419-8424
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number22
DOIs
StatePublished - May 30 2006

Keywords

  • Cell junctions
  • Organogenesis
  • Transcription

ASJC Scopus subject areas

  • General

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