Lung mesenchymal expression of Sox9 plays a critical role in tracheal development
Identifieur interne : 003487 ( Main/Exploration ); précédent : 003486; suivant : 003488Lung mesenchymal expression of Sox9 plays a critical role in tracheal development
Auteurs : Gianluca Turcatel [États-Unis] ; Nicole Rubin [États-Unis] ; Douglas B. Menke [États-Unis] ; Gary Martin [États-Unis] ; Wei Shi [États-Unis] ; David Warburton [États-Unis]Source :
- BMC Biology [ 1741-7007 ] ; 2013.
Abstract
Embryonic lung development is instructed by crosstalk between mesenchyme and epithelia, which results in activation of transcriptional factors, such as
Transgenic mice lacking
The appropriate temporospatial expression of
Url:
DOI: 10.1186/1741-7007-11-117
PubMed: 24274029
PubMed Central: 4222279
Affiliations:
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Le document en format XML
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plays a critical role in tracheal development</title>
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>Embryonic lung development is instructed by crosstalk between mesenchyme and epithelia, which results in activation of transcriptional factors, such as <italic>Sox9</italic>
, in a temporospatial manner. <italic>Sox9</italic>
is expressed in both distal lung epithelium and proximal lung mesenchyme. Here, we investigated the effect of lung mesenchyme-specific inducible deletion of <italic>Sox9</italic>
during murine lung development.</p>
</sec>
<sec><title>Results</title>
<p>Transgenic mice lacking <italic>Sox9</italic>
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. <italic>In situ</italic>
hybridization showed an altered expression pattern of <italic>Tbx4</italic>
, <italic>Tbx5</italic>
and <italic>Fgf10</italic>
genes and marked reduction of <italic>Collagen2</italic>
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 <italic>Sox9</italic>
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.</p>
</sec>
<sec><title>Conclusion</title>
<p>The appropriate temporospatial expression of <italic>Sox9</italic>
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.</p>
</sec>
</div>
</front>
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