Hepatocyte nuclear factor-3β limits cellular diversity in the developing respiratory epithelium and alters lung morphogenesis in vivo

Lan Zhou, Chitta R. Dey, Susan E. Wert, Cong Yan, Robert H. Costa, Jeffrey A. Whitsett

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Hepatocyte nuclear factor-3β (HNF-3β), a nuclear protein of the winged helix family of transcription factors, is known to play a critical role in the formation of the embryonic node, notochord, and foregut endoderm. HNF- 3β influences the expression of a number of target genes in the respiratory epithelium, activating transcription of thyroid transcription factor-1, surfactant protein-B and clara cell secretory protein. In order to discern the role of HNF-3β in differentiation and gene expression in the lung, HNF- 3β was expressed in developing respiratory epithelial cells of transgenic mice, under the control of the human surfactant protein C gene promoter. Pulmonary abnormalities were observed in the lungs of fetal mice bearing the HNF-3β transgene. Differentiation of distal respiratory epithelial cells was arrested in the early pseudoglandular stage. Branching morphogenesis and vasculogenesis were markedly disrupted in association with decreased E- cadherin and vascular endothelial growth factor expression. HNF-3β limits cellular diversity of developing respiratory epithelium and alters lung morphogenesis in vivo, suggesting that precise temporal-spatial regulation of HNF-3β expression is critical for respiratory epithelial cell differentiation and lung morphogenesis.

Original languageEnglish (US)
Pages (from-to)305-314
Number of pages10
JournalDevelopmental Dynamics
Volume210
Issue number3
DOIs
StatePublished - Nov 1997

Keywords

  • HNF-3β
  • Lung morphogenesis
  • Respiratory epithelial cell differentiation
  • Transgenic mice

ASJC Scopus subject areas

  • Developmental Biology

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