The essential role of primary cilia in lung development
Research Poster Health & Life Sciences 2025 Graduate ExhibitionPresentation by Shimaa Ali
Exhibition Number 182
Abstract
Congenital lung malformations (CLMs) are developmental anomalies of the lung that can be fatal at birth in their critical form. Understanding lung development is essential for uncovering the causes of lung defects, enabling early diagnosis, and potential therapies. Lung development depends on continuous interactions between the endoderm and the adjacent mesenchyme. This communication regulates the expression of many signaling pathways. The primary cilium, a non-motile, microtubule-based organelle in most vertebrate cells, is a crucial mediator of some of these signaling pathways. Dysfunction in primary cilia results in a range of conditions known as ciliopathies. However, the specific role of primary cilia in mammalian lung development has not been thoroughly investigated. To determine the absolute requirement of primary cilia for lung development, we employed global Ift20 and Ift88 knockout mouse models. We found that global deletion of Ift20 or Ift88 disrupts lung Nkx2.1+ progenitor formation, suggesting the crucial role of primary cilia in early lung development. Because cilia are present in both mesenchymal and epithelial compartments, we took advantage of tissue-specific knockouts to determine whether cilia are required in the epithelium, the mesenchyme, or both for lung development. We found that the loss of mesenchymal cilia resulted in lung defects while the loss of epithelial cilia did not affect lung development. In conclusion, our study highlights the absolute requirement of cilia in lung development, their specific role within different lineages during lung development, and provides insights into the mechanisms underlying the CLMs.
Importance
Lung development involves a complex interplay of genetic, molecular, and cellular events that orchestrate the formation and maturation of this vital organ. Disruptions in these processes can lead to congenital lung abnormalities and respiratory disorders, which can be fatal at birth in their most critical forms. A deeper understanding of these processes will help uncover the mechanisms underlying lung defects and diseases, facilitating early diagnosis and potential therapeutic strategies. My research investigates the role of primary cilia in lung development, aiming to elucidate how their dysfunction contributes to congenital respiratory disorders. By studying primary cilia, I hope to provide critical insights into the underlying causes of these conditions, ultimately advancing our ability to diagnose and treat them effectively.