# YAP/TAZ-NRG1 crosstalk in airway epithelial cell fate control

> **NIH NIH F31** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2020 · $45,520

## Abstract

Abstract:
Lung diseases are among the most common medical conditions worldwide. A hallmark of many lung diseases
is aberrant polarity of the lung epithelium; disrupted lung epithelial cell architecture has been observed in several
diseases including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and
cystic fibrosis. Healthy luminal cells in the airways of the lung exhibit distinct apical-basal polarity, and a major
regulator of cell polarity is the Crumbs complex, which is organized by the transmembrane Crumbs proteins. Our
preliminary data has shown that loss of Crumbs3 (Crb3), the isoform predominantly expressed in the lung, in the
luminal cells of the airway epithelium in adult mice leads to dramatic cell fate defects. These airways form lesions
of stratified cells that express markers of basal cells, which are stem cells of the lung airway epithelium that
normally act to repair damage. Using lineage tracing, our data suggest that conditional deletion of Crb3 results
in both de-differentiation and non-cell-autonomous signaling that leads to basal cell expansion. We have also
demonstrated that combined deletion of Yap and Taz, the transcriptional effectors of the Hippo pathway, is
sufficient to revert the formation of these lesions. Our preliminary RNA-seq profiling of lung epithelial cells has
revealed neuregulin-1 (Nrg1) as a transcriptional target of Yap/Taz. This is in accordance with our mouse model,
which shows increased levels of Nrg1 mRNA in Crb3-deleted lesions. Nrg1 is classically an activator of the ErbB
family of membrane receptors, but there is also evidence suggesting it activates Yap transcriptional activity. Our
goals are to: 1) define the regulatory relationship between Yap/Taz and Nrg1/ErbB signaling in promoting the
growth of basal airway epithelial cells; and 2) determine the importance of Nrg1/ErbB and its downstream
signaling in the formation and maintenance of Crb3-null basal cell lesions in vivo. Collectively, our proposed
studies will provide important insight into the signaling events downstream of defective cell polarity, which will
improve our understanding of the variety of lung diseases in which it is implicated.

## Key facts

- **NIH application ID:** 9882889
- **Project number:** 5F31HL146163-02
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Nathan Kingston
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $45,520
- **Award type:** 5
- **Project period:** 2019-03-01 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9882889

## Citation

> US National Institutes of Health, RePORTER application 9882889, YAP/TAZ-NRG1 crosstalk in airway epithelial cell fate control (5F31HL146163-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9882889. Licensed CC0.

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