T‐box gene products are required for mesenchymal induction of epithelial branching in the embryonic mouse lung

JA Cebra‐Thomas, J Bromer, R Gardner… - … dynamics: an official …, 2003 - Wiley Online Library
JA Cebra‐Thomas, J Bromer, R Gardner, GK Lam, H Sheipe, SF Gilbert
Developmental dynamics: an official publication of the American …, 2003Wiley Online Library
The regulation of signaling pathways is a prerequisite for coordinating the induction
between mesenchymal and epithelial tissues during morphogenesis. Mesenchymal FGF10
is known to be an important paracrine factor regulating the branching morphogenesis of the
bronchial epithelium. By using antisense oligonucleotides (AS ODNs) and in vitro culture of
embryonic lungs, we demonstrate that the transcription factors Tbx4 and Tbx5 are critical for
the expression of mesenchymal FGF10. Treatment of embryonic lung cultures with AS ODNs …
Abstract
The regulation of signaling pathways is a prerequisite for coordinating the induction between mesenchymal and epithelial tissues during morphogenesis. Mesenchymal FGF10 is known to be an important paracrine factor regulating the branching morphogenesis of the bronchial epithelium. By using antisense oligonucleotides (AS ODNs) and in vitro culture of embryonic lungs, we demonstrate that the transcription factors Tbx4 and Tbx5 are critical for the expression of mesenchymal FGF10. Treatment of embryonic lung cultures with AS ODNs to Tbx4 and Tbx5 reduces the level of these transcripts, suppresses Fgf10 expression in the mesenchyme, and completely eliminates the formation of new lung branches. If FGF10 is locally replaced in these AS ODN‐treated lungs, epithelial branching is restored. These studies provide evidence that the production of branching signals by the lung mesenchyme is mediated by T‐box genes. © 2002 Wiley‐Liss, Inc.
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