bioRxiv
[Preprint]. 2025 Feb 14:2025.02.13.635155.
doi: 10.1101/2025.02.13.635155. https://pubmed.ncbi.nlm.nih.gov/39990361/
MYRF is Essential in Mesothelial Cells to Promote Lung Development and Maturation
Gidsela Luna, Jamie Verheyden, Chunting Tan, Estelle Kim, Michelle Hwa, Jugraj Sahi, Yufeng Shen, Wendy Chung, David McCulley, Xin Sun
- PMID: 39990361
- PMCID: PMC11844445
- DOI: 10.1101/2025.02.13.635155
Abstract
The mesothelium is a squamous monolayer that ensheathes internal organs, lines the body cavity, and the diaphragm. It serves as a protective barrier, coated in glycocalyx, and secretes lubricants to facilitate tissue movement. How the mesothelium forms is poorly understood. Here, we investigate Myrf , a transcription factor gene expressed in the mesothelium, because it carries variants in patients with Congenital Diaphragmatic Hernia (CDH), a disorder that affects the diaphragm, lung, and other organs. In mice, inactivation of Myrf early in organogenesis resulted in CDH and defective mesothelial specification, compromising its function as a signaling center for lung growth. Inactivation of Myrf later led to enhanced mesothelium differentiation into mesenchymal cell types through partial epithelial-to-mesenchymal transition (EMT), resulting in a unique accumulation of smooth muscle encasing the lung. In this role, MYRF functions in parallel with YAP/TAZ. Together, these findings establish MYRF as a critical regulator of mesothelium development, and when mutated, causes CDH.
