T-box gene products are required for mesenchymal induction of epithelial branching in the embryonic mouse lung.
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.
Cebra-Thomas
Judith A
JA
Department of Biology, Franklin and Marshall College, Lancaster, Pennsylvania, USA. jacebra@hotmail.com
Bromer
Jason
J
Gardner
Rose
R
Lam
Gordon K
GK
Sheipe
Hillary
H
Gilbert
Scott F
SF
D000818:Animals; D004848:Epithelium / Q000196:embryology*; D051526:Fibroblast Growth Factor 10; D005346:Fibroblast Growth Factors / Q000096:biosynthesis / Q000378:metabolism; D053823:Hedgehog Proteins; D017403:In Situ Hybridization; D008168:Lung / Q000196:embryology*; D008648:Mesoderm / Q000378:metabolism*; D051379:Mice; D009024:Morphogenesis; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000096:biosynthesis / Q000502:physiology*; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism
C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D053823:Hedgehog Proteins; D016376:Oligonucleotides, Antisense; C465570:Shh protein, mouse; C097348:T-Box Domain Protein 2; D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5; C103177:Tbx4 protein, mouse; D015534:Trans-Activators; D005346:Fibroblast Growth Factors