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MYRF controls mesothelium specification, signaling, and plasticity in lung development
Gidsela Luna1, Jamie M Verheyden1, Chunting Tan1
1Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA; Department of Cell and Developmental Biology, School of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Developmental Cell
|January 20, 2026
Summary
Myelin regulatory factor (Myrf) is crucial for mesothelium development and lung growth. Its disruption causes congenital diaphragmatic hernia and mimics adult lung fibrosis, revealing complex roles in development and disease.
Area of Science:
- Developmental biology
- Cell biology
- Medical research
Background:
- The mesothelium, a vital organ lining, has poorly understood functions beyond tissue gliding.
- Congenital diaphragmatic hernia (CDH) is a developmental disorder linked to mutations in the myelin regulatory factor (Myrf) gene.
Purpose of the Study:
- To investigate the role of Myrf in mesothelium development and its connection to CDH.
- To explore Myrf's function in lung development and its potential link to fibrotic lung diseases.
Main Methods:
- Utilized mouse models with targeted Myrf inactivation at different embryonic stages.
- Analyzed mesothelium specification, lung development, and cellular differentiation.
- Investigated the synergistic interaction between Myrf and YAP/TAZ signaling pathways.
Main Results:
- Early Myrf inactivation in mice led to CDH and impaired mesothelium signaling for lung growth.
- Later Myrf inactivation caused excessive differentiation into elastin-producing cells, mimicking pleuroparenchymal fibroelastosis (PPFE).
- Myrf acts synergistically with YAP/TAZ in mesothelium differentiation.
Conclusions:
- Myrf plays a critical, stage-dependent role in mesothelium development and lung organogenesis.
- Myrf dysfunction contributes to both congenital diaphragmatic hernia and fibrotic lung conditions.
- This study elucidates the mesothelium's complex involvement in development and disease pathogenesis.
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