Tracheal occlusion increases the rate of epithelial branching of embryonic mouse lung via the FGF10-FGFR2b-Sprouty2 pathway.
Tracheal occlusion during lung development accelerates growth in response to increased intraluminal pressure. In order to investigate the role of internal pressure on murine early lung development, we cauterized the tip of the trachea, to occlude it, and thus to increase internal pressure. This method allowed us to evaluate the effect of tracheal occlusion on the first few branch generations and on gene expression. We observed that the elevation of internal pressure induced more than a doubling in branching, associated with increased proliferation, while branch elongation speed increased 3-fold. Analysis by RT-PCR showed that Fgf10, Vegf, Sprouty2 and Shh mRNA expressions were affected by the change of intraluminal pressure after 48h of culture, suggesting mechanotransduction via internal pressure of these key developmental genes. Tracheal occlusion did not increase the number of branches of Fgfr2b-/- mice lungs nor of wild type lungs cultured with Fgfr2b antisense RNA. Tracheal occlusion of Fgf10(LacZ/-) hypomorphic lungs led to the formation of fewer branches than in wild type. We conclude that internal pressure regulates the FGF10-FGFR2b-Sprouty2 pathway and thus the speed of the branching process. Therefore pressure levels, fixed both by epithelial secretion and boundary conditions, can control or modulate the branching process via FGF10-FGFR2b-Sprouty2.
Unbekandt
Mathieu
M
Groupe Matière Condensée et Matériaux, Université de Rennes 1, 35042 Rennes, France.
del Moral
Pierre-Marie
PM
Sala
Frederic G
FG
Bellusci
Saverio
S
Warburton
David
D
Fleury
Vincent
V
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D051526:Fibroblast Growth Factor 10 / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D047908:Intracellular Signaling Peptides and Proteins; D008168:Lung / Q000098:blood supply / Q000196:embryology* / Q000378:metabolism; D040542:Mechanotransduction, Cellular; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D009024:Morphogenesis / Q000235:genetics; D018919:Neovascularization, Physiologic / Q000235:genetics; D011312:Pressure; D017346:Protein Serine-Threonine Kinases; D016372:RNA, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000037:antagonists & inhibitors / Q000235:genetics*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000196:embryology; D014132:Trachea / Q000196:embryology*
D048868:Adaptor Proteins, Signal Transducing; C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016372:RNA, Antisense; D012333:RNA, Messenger; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017346:Protein Serine-Threonine Kinases; C118389:Spry2 protein, mouse