# Determining the Role of Myrf in the Lung Mesothelium

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $38,965

## Abstract

PROJECT SUMMARY/ABSTRACT
 The mesothelium is a monolayer of mesoderm-derived epithelial cells that encapsulates many of our
internal organs, including the lung. Its ascribed role is to prevent friction as internal organs slide against each
other and the body wall. Whether it plays other roles in development and homeostasis is poorly understood. In
this study, I will investigate mesothelium function through interrogating the role of Myrf, a transcription factor
gene expressed in the mesothelium of various organs, including the lung during development. I approached
Myrf because variants in this gene have been identified in congenital diaphragmatic hernia (CDH), a birth
defect associated with lung hypoplasia and pulmonary hypertension. I have found that inactivation of Myrf at
the start of lung development resulted in a striking CDH phenotype accompanied by pulmonary hypoplasia
prior to diaphragm closure. The expression of Fgf9, a key growth factor expressed in the mesothelium is
reduced, suggesting that Myrf function in the mesothelium is to control mesothelium function as a source of
signals. In comparison, inactivation of Myrf later on at the branching stage resulted in the expansion of the
mesothelium into multiple cell layers. This is strikingly reminiscent of the phenotype when Hippo pathway
kinase genes Lats 1/2 were inactivated in the epicardium, a mesothelium-equivalent cell layer in the heart.
Consistent with an involvement of Hippo pathway, YAP, a downstream transcription effector, was found
increased in the nucleus of the excess mesothelial cells in the Myrf mutant. These findings led me to propose
that during development, Myrf controls mesothelium function by regulating the expression of growth signals
(Aim 1) and components of the Hippo-YAP signaling pathway (Aim 2). Since pulmonary hypoplasia is a key
cause of mortality in CDH patients, my findings will advance our knowledge on CDH disease mechanism.

## Key facts

- **NIH application ID:** 10315975
- **Project number:** 1F31HL160204-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Gidsela Luna
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,965
- **Award type:** 1
- **Project period:** 2021-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10315975

## Citation

> US National Institutes of Health, RePORTER application 10315975, Determining the Role of Myrf in the Lung Mesothelium (1F31HL160204-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10315975. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*