Carmona, R., Cañete, A., Cano, E., Ariza, L., Rojas, A. and Muñoz-Chápuli, R. (2016) Conditional deletion of WT1 in the septum transversum mesenchyme causes congenital diaphragmatic hernia in mice. eLife, 5, e16009. (doi: 10.7554/eLife.16009) (PMID:27642710) (PMCID:PMC5028188)
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Abstract
Congenital diaphragmatic hernia (CDH) is a severe birth defect. Wt1-null mouse embryos develop CDH but the mechanisms regulated by WT1 are unknown. We have generated a murine model with conditional deletion of WT1 in the lateral plate mesoderm, using the G2 enhancer of the Gata4 gene as a driver. 80% of G2-Gata4Cre;Wt1fl/fl embryos developed typical Bochdalek-type CDH. We show that the posthepatic mesenchymal plate coelomic epithelium gives rise to a mesenchyme that populates the pleuroperitoneal folds isolating the pleural cavities before the migration of the somitic myoblasts. This process fails when Wt1 is deleted from this area. Mutant embryos show Raldh2 downregulation in the lateral mesoderm, but not in the intermediate mesoderm. The mutant phenotype was partially rescued by retinoic acid treatment of the pregnant females. Replacement of intermediate by lateral mesoderm recapitulates the evolutionary origin of the diaphragm in mammals. CDH might thus be viewed as an evolutionary atavism.
| Item Type: | Articles |
|---|---|
| Additional Information: | This study was funded by grants BFU2014- 52299-P (Spanish Ministry of Economy), ISCIII-RD12/0019-0022 (ISCIII-TERCEL), and P11-CTS-07564 (Junta de Andalucia). AR is the recipient of the grant PI14-00804 funded by Instituto de Salud Carlos III and cofounded by FEDER funding. |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Canete Sanchez, Mrs Ana Elodia |
| Authors: | Carmona, R., Cañete, A., Cano, E., Ariza, L., Rojas, A., and Muñoz-Chápuli, R. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | eLife |
| Publisher: | eLife Sciences Publications |
| ISSN: | 2050-084X |
| ISSN (Online): | 2050-084X |
| Copyright Holders: | Copyright © 2016 Carmona et al. |
| First Published: | First published in eLife 5:e16009 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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