RT Journal Article
T1 Conditional deletion of WT1 in the septum transversum mesenchyme causes congenital diaphragmatic hernia in mice
A1 Carmona-Mejías, Rita María
A1 Cañete, A
A1 Cano, E
A1 Ariza, L
A1 Rojas, A
A1 Muñoz-Chápuli, R
K1 Hernia diafragmática
AB 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.
PB Elife
YR 2016
FD 2016-09
LK https://hdl.handle.net/10630/34022
UL https://hdl.handle.net/10630/34022
LA eng
NO Rita CarmonaAna CañeteElena CanoLaura ArizaAnabel RojasRamon Muñoz-Chápuli (2016) Conditional deletion of WT1 in the septum transversum mesenchyme causes congenital diaphragmatic hernia in mice eLife 5:e16009. https://doi.org/10.7554/eLife.16009
NO This paper was supported by the following grants:Ministerio de Economía y Competitividad BFU2014-52299-P to Rita Carmona, Ana Cañete, Laura Ariza, Ramon Muñoz-Chápuli.Instituto de Salud Carlos III ISCIII-RD12/0019-0022 (ISCIII-TERCEL) to Rita Carmona, Ana Cañete, Elena Cano, Laura Ariza, Anabel Rojas, Ramon Muñoz-Chápuli.Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía P11-CTS-07564 to Rita Carmona, Ana Cañete, Elena Cano, Laura Ariza, Ramon Muñoz-Chápuli.Instituto de Salud Carlos III PI14-00804 to Anabel Rojas
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 21 ene 2026