Hepatocyte nuclear factor-3β limits cellular diversity in the developing respiratory epithelium and alters lung morphogenesis in vivo
✍ Scribed by Lan Zhou; Chitta R. Dey; Susan E. Wert; Cong Yan; Robert H. Costa; Jeffrey A. Whitsett
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 738 KB
- Volume
- 210
- Category
- Article
- ISSN
- 1058-8388
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✦ Synopsis
Hepatocyte nuclear factor-3 (HNF-3), 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-3 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-3 in differentiation and gene expression in the lung, HNF-3 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-3 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-3 limits cellular diversity of developing respiratory epithelium and alters lung morphogenesis in vivo, suggesting that precise temporalspatial regulation of HNF-3 expression is critical for respiratory epithelial cell differentiation and lung morphogenesis.