FOR decades, researchers believed that alveoli, the tiny air sacs responsible for gas exchange, formed by airspace subdivision via ingrowing septa. However, a recent study using advanced imaging technology has revealed a new mechanism: alveoli actually develop through epithelial outgrowths, supported by contracting mesenchymal ring structures.
To capture this process, researchers employed scanned oblique-plane illumination microscopy to observe lung development in real-time. This high-resolution, long-term imaging of living lung slices allowed them to track epithelial and mesenchymal cell behaviors, leading to a groundbreaking computational model of alveologenesis.
Understanding these mechanisms is crucial, as the gas-exchange surface of the lungs expands more than 20-fold during the alveolar stage—spanning from late gestation through early adolescence. The findings not only reshape our understanding of lung organogenesis but also have significant implications for lung regeneration therapies.
By leveraging this new model, researchers can now analyze how different factors, such as disruptions in intercellular signaling pathways, affect alveologenesis. This research could pave the way for innovative treatments to support lung repair and regeneration in patients with respiratory diseases.
Reference: Negretti NM et al. Epithelial outgrowth through mesenchymal rings drives lung alveologenesis. JCI Insight. 2025;10(4):e187876.
Rob Hancox | AMJ
