Lung mesenchymal expression of Sox9plays a critical role in tracheal development

BMC Biology

Research Article

Gary Martin¹  Douglas B Menke²  Wei Shi³  Gianluca Turcatel³  Nicole Rubin³  David Warburton³ 

[1]Department of Biosciences, Occidental College, 1600 Campus Road, 90041, Los Angeles, CA, USA

[2]Department of Genetics, University of Georgia, 120 East Green Street, 30602, Athens, GA, USA

[3]Developmental Biology and Regenerative Medicine Program, Saban Research Institute, Children’s Hospital Los Angeles, Keck School of Medicine and Ostrow School of Dentistry, University of Southern California, 4661 Sunset Boulevard, 90027, Los Angeles, CA, USA

关键词: Sox9;    Trachea;    Lung;    Cartilage;    CC10;    P63;   

DOI  :  10.1186/1741-7007-11-117

 received in 2013-11-05, accepted in 2013-11-22,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundEmbryonic 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.ResultsTransgenic 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.ConclusionThe 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.

【 授权许可】

Unknown   
© Turcatel et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.