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Updated: Aug 26, 2025
11:48
Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
Published on: October 9, 2014
13.0K
Aerocyte specification and lung adaptation to breathing is dependent on alternative splicing changes
Marta F Fidalgo1, Catarina G Fonseca1, Paulo Caldas2
1Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
Life Science Alliance
|October 11, 2022
Summary
Lung development involves coordinated cell communication. This study reveals a key splicing switch in vascular endothelial growth factor A (VEGF-A) in alveolar cells, essential for adapting lungs to breathing after birth.
Area of Science:
- Developmental Biology
- Molecular Biology
- Pulmonary Medicine
Background:
- Alveolar development is crucial for lung function and requires cell-cell communication.
- The precise mechanisms modulating this crosstalk for breathing adaptation remain unclear.
Purpose of the Study:
- To investigate the regulation of cell-type-specific gene expression during lung development.
- To understand the role of alternative splicing in lung adaptation to breathing.
Main Methods:
- Analysis of alternative splicing events in developing mouse lungs.
- Identification of splicing regulators (hnRNP A1, Cpeb4, Elavl2/HuB).
- Functional studies on vascular endothelial growth factor A (VEGF-A) isoforms in alveolar epithelial cells.
Main Results:
- A synchronous alternative splicing switch occurs in developing mouse lungs at birth.
- Vascular endothelial growth factor A (VEGF-A) switches from the 164 to the 188 isoform specifically in alveolar epithelial AT1 cells.
- VEGF-A 188 isoform drives the specification of gas exchange-specialized aerocytes.
Conclusions:
- Cell-type-specific regulation of VEGF-A alternative splicing is critical for lung development.
- This splicing switch modulates epithelial-endothelial crosstalk, promoting lung adaptation to breathing.
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