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bioRxiv · 10.1101/2025.02.13.635155

MYRF is Essential in Mesothelial Cells to Promote Lung Development and Maturation

Luna, G.·Verheyden, J.·Tan, C.·Kim, E.·Hwa, M.·Sahi, J.·Shen, Y.·Chung, W.·McCulley, D.·Sun, X.
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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.

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Luna, G., Verheyden, J., Tan, C., Kim, E., Hwa, M., Sahi, J., Shen, Y., Chung, W., McCulley, D., Sun, X.. 2025-02-14. MYRF is Essential in Mesothelial Cells to Promote Lung Development and Maturation. https://doi.org/10.1101/2025.02.13.635155

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