2026-04-29T04:10:20Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/171562024-09-22T00:05:16Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud
author
Carmona, Rita
author
Cañete, Ana
author
Cano, Elena
author
Ariza, Laura
author
Rojas, Anabel
author
Muñoz-Chápuli, Ramon
authoraffiliation
[Carmona, Rita] Univ Malaga, Dept Anim Biol, Malaga, Spain
authoraffiliation
[Canete, Ana] Univ Malaga, Dept Anim Biol, Malaga, Spain
authoraffiliation
[Ariza, Laura] Univ Malaga, Dept Anim Biol, Malaga, Spain
authoraffiliation
[Munoz-Chapuli, Ramon] Univ Malaga, Dept Anim Biol, Malaga, Spain
authoraffiliation
[Carmona, Rita] Andalusian Ctr Nanomed & Biotechnol BIONAND, Malaga, Spain
authoraffiliation
[Canete, Ana] Andalusian Ctr Nanomed & Biotechnol BIONAND, Malaga, Spain
authoraffiliation
[Ariza, Laura] Andalusian Ctr Nanomed & Biotechnol BIONAND, Malaga, Spain
authoraffiliation
[Munoz-Chapuli, Ramon] Andalusian Ctr Nanomed & Biotechnol BIONAND, Malaga, Spain
authoraffiliation
[Cano, Elena] Max Delbruck Ctr Mol Med, Berlin, Germany
authoraffiliation
[Rojas, Anabel] Andalusian Ctr Mol Biol & Regenerat Med CABIMER, Seville, Spain
authoraffiliation
[Rojas, Anabel] Ctr Invest Biomed Red Diabet & Enfermedades Metab, Seville, Spain
2024-01-16T12:16:31Z
2024-01-16T12:16:31Z
2016-09-19
http://hdl.handle.net/10668/10457
http://hdl.handle.net/20.500.12105/17156
27642710
10.7554/eLife.16009
2050-084X
eLife
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-Gata4(Cre);Wt1(fl/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.
eng
Gata4
Wilms' tumor suppressor gene
congenital diaphragmatic hernia
developmental biology
epithelial-mesenchymal transition
human biology
medicine
mouse
stem cells
Conditional deletion of WT1 in the septum transversum mesenchyme causes congenital diaphragmatic hernia in mice.
research article