ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2025
Mesenchymal retinoic acid signaling is required for normal diaphragm development in mice.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Modeling patient variants ofbioRxiv : the preprint server for biology · 2026Article
- Epithelial Dysfunction in Congenital Diaphragmatic Hernia: Mechanisms, Models and Emerging Therapies.Cells · 2025Review
- Mesenchymal retinoic acid signaling is required for normal diaphragm development in mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Mitochondrial Lon Peptidase 1 Controls Diaphragm and Lung Development in a Context-Dependent Manner.Journal of respiratory biology and translational medicine · 2025Article
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Authors and funding
6 authors.
Funding
Abstract
Congenital diaphragmatic hernia (CDH) is characterized by incomplete formation of the diaphragm, causing herniation of the abdominal organs and subsequent lung hypoplasia; however, the etiology of CDH is poorly understood. The Retinoid Hypothesis posits that abnormal retinoic acid signaling leads to the formation of diaphragmatic hernias. Our goal is to better understand diaphragm development and the etiology of CDH. To achieve this goal, we first performed single-cell RNA sequencing analysis of the developing diaphragm, then generated a conditional retinoic acid receptor dominant negative knock-in to inhibit retinoic acid signaling in the mesenchyme of the developing diaphragm. Our single-cell RNA sequencing analysis revealed 10 distinct cell populations in the developing diaphragm, with mesenchymal cells being the primary expresser of CDH and retinoic acid signaling-related genes. Transgenic inhibition of mesenchymal retinoic acid signaling in the developing diaphragm caused hernias in 100% of embryos, recapitulating the hallmarks of CDH. Overall, our studies show that retinoic acid signaling in the mesenchymal component of the diaphragm is required for normal diaphragm development.
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