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Published on: October 16, 2016
HuR controls lung branching morphogenesis and mesenchymal FGF networks
Nikos Sgantzis1, Anthie Yiakouvaki, Eumorphia Remboutsika
1Institute of Immunology, Biomedical Sciences Research Center "Alexander Fleming", 16672 Vari, Greece.
The RNA-binding protein HuR is crucial for lung development, regulating mesenchymal responses during branching. Its absence disrupts lung morphogenesis by affecting FGF10 and Tbx4 mRNA levels, highlighting its role in post-transcriptional gene regulation.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Lung development relies on complex regulatory networks involving mesenchymal-epithelial interactions.
- While transcription factors and signaling molecules are studied, post-transcriptional regulation remains less understood.
Purpose of the Study:
- To investigate the role of RNA-binding protein HuR in lung development and mesenchymal-epithelial interactions.
- To determine if HuR is essential for lung branching morphogenesis.
Main Methods:
- Conditional deletion of HuR in epiblast and epithelial progenitors in mice.
- Analysis of lung morphology and gene expression (FGF10, Tbx4).
- Assessment of rescue experiments using exogenous FGF10.
Main Results:
- Epiblast-specific deletion of HuR blocked distal bronchial branching during the pseudoglandular stage.
- HuR deletion impaired mesenchymal responses, not epithelial development.
- Loss of HuR reduced FGF10 and Tbx4 mRNA levels, which were rescued by exogenous FGF10.
- HuR controls Fgf10 and Tbx4 mRNA stability, mediating FGF9-induced regulation.
Conclusions:
- HuR is the first identified RNA-binding protein essential for lung development.
- HuR acts as a key post-transcriptional regulator of mesenchymal signaling pathways during lung branching morphogenesis.
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