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dc.contributor.authorTurcatel, Gianluca
dc.contributor.authorRubin, Nicole
dc.contributor.authorMenke, Douglas B
dc.contributor.authorMartin, Gary
dc.contributor.authorShi, Wei
dc.contributor.authorWarburton, David
dc.date.accessioned2014-06-19T20:13:30Z
dc.date.available2014-06-19T20:13:30Z
dc.date.issued2013-11-25
dc.identifier.citationBMC Biology. 2013 Nov 25;11(1):117
dc.identifier.urihttp://dx.doi.org/10.1186/1741-7007-11-117
dc.identifier.urihttp://hdl.handle.net/10724/29881
dc.description.abstractAbstract Background Embryonic lung development is instructed by crosstalk between mesenchyme and epithelia, which results in activation of transcriptional factors, such as Sox9, in a temporospatial manner. Sox9 is expressed in both distal lung epithelium and proximal lung mesenchyme. Here, we investigated the effect of lung mesenchyme-specific inducible deletion of Sox9 during murine lung development. Results Transgenic mice lacking Sox9 expression were unable to breathe and died at birth, with noticeable tracheal defects. Cartilage rings were missing, and the tracheal lumen was collapsed in the mutant trachea. In situ hybridization showed an altered expression pattern of Tbx4, Tbx5 and Fgf10 genes and marked reduction of Collagen2 expression in the tracheal mesenchyme. The tracheal phenotype was increasingly severe, with longer duration of deletion. Lymphatic vasculature was underdeveloped in the mutant trachea: Prox1, Lyve1, and Vegfr3 were decreased after Sox9 knockout. We also found that compared with normal tracheal epithelium, the mutant tracheal epithelium had an altered morphology with fewer P63-positive cells and more CC10-positive cells, fewer goblet cells, and downregulation of surfactant proteins A and C. Conclusion The appropriate temporospatial expression of Sox9 in lung mesenchyme is necessary for appropriate tracheal cartilage formation, lymphatic vasculature system development, and epithelial differentiation. We uncovered a novel mechanism of lung epithelium differentiation: tracheal cartilage rings instruct the tracheal epithelium to differentiate properly during embryonic development. Thus, besides having a mechanical function, tracheal cartilage also appears to be a local signaling structure in the embryonic lung.
dc.titleLung mesenchymal expression of Sox9 plays a critical role in tracheal development
dc.typeJournal Article
dc.date.updated2014-04-03T13:56:03Z
dc.description.versionPeer Reviewed
dc.language.rfc3066en
dc.rights.holderGianluca Turcatel et al.; licensee BioMed Central Ltd.


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