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Hepatocyte nuclear factor‐3β limits cellular diversity in the developing respiratory epithelium and alters lung morphogenesis in vivo
Author(s) -
Zhou Lan,
Dey Chitta R.,
Wert Susan E.,
Yan Cong,
Costa Robert H.,
Whitsett Jeffrey A.
Publication year - 1997
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/(sici)1097-0177(199711)210:3<305::aid-aja10>3.0.co;2-9
Subject(s) - biology , endoderm , morphogenesis , microbiology and biotechnology , respiratory epithelium , hepatocyte growth factor , transcription factor , epithelium , wnt signaling pathway , hepatocyte nuclear factors , cellular differentiation , gene , genetics , signal transduction , receptor
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. Dev. Dyn. 1997;210: 305–314. © 1997 Wiley‐Liss, Inc.