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T‐box gene products are required for mesenchymal induction of epithelial branching in the embryonic mouse lung
Author(s) -
CebraThomas Judith A.,
Bromer Jason,
Gardner Rose,
Lam Gordon K.,
Sheipe Hillary,
Gilbert Scott F.
Publication year - 2003
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/dvdy.10208
Subject(s) - mesenchyme , biology , paracrine signalling , mesenchymal stem cell , microbiology and biotechnology , embryonic stem cell , fgf10 , morphogenesis , in situ hybridization , lung , immunology , gene expression , gene , genetics , medicine , receptor
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.