File:Model Sox9 lung development 01.jpg

Model Sox9 Lung Development

Lung mesenchymal expression of Sox9 plays a critical role in tracheal development BMC Biol. 2013 Nov 25;11:117. doi: 10.1186/1741-7007-11-117.

Turcatel G, Rubin N, Menke DB, Martin G, Shi W, Warburton D1.

Abstract

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.

PMID 24274029

http://bmcbiol.biomedcentral.com/articles/10.1186/1741-7007-11-117

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Figure 10 Concept diagram of Sox9 function in lung development. Sox9 acts downstream of Tbx4/5[6]. Sox9 feeds back negatively on Tbx4 and Tbx5 in the tracheal mesenchyme. Cartilage ring formation requires functional Sox9 expression in the tracheal mesenchyme. Lack of cartilage rings induce altered tracheal epithelium differentiation (increased Clara cells, and decreased basal and goblet cells) and defective development of tracheal vasculature structurest.