Year: 2025
Type: article
Abstract: ABSTRACT Airway multiciliated cells (MCs) maintain respiratory health by clearing mucus and trapped particles through the beating of motile cilia. While it is known that ciliary lengths decrease along the proximal-distal (P-D) axis of the tracheobronchial tree, how this is regulated is unclear. Here, we demonstrate that canonical Notch signaling in MCs plays a critical role in stabilizing ciliary length. Inhibition of Notch signaling in MCs results in ciliary shortening in the trachea, lengthening in the distal airway, and to region-specific alterations in gene expression. We probe how environmental challenges impact MC homeostasis using germ-free and Mycobacterium tuberculosis ( M. tb ) infection models. While germ-free conditions do not perturb ciliary lengths, M. tb infection leads to lengthening of distal airway cilia, correlating with a downregulation of Notch signaling. These findings reveal that ciliary length and the P-D gradient in the airways are actively regulated, with Notch signaling serving as a stabilizing mechanism.
Source: Life Science Alliance
Authors: Neenu Joy, Aditya Deshpande, Sai Manoz Lingamallu, Vasam Manjveekar Prabantu, CN Naveenkumar, K Bharathkumar, Sukanya Bhat, Zabdiel Alvarado-Martinez, Alessandra Livraghi-Butrico, James S. Hagood, Richard C. Boucher, Daniel Lafkas, Kevin M. Byrd, Shridhar Narayanan, R.K. Shandil, Arjun Guha
Institutions: Institute for Stem Cell Biology and Regenerative Medicine, SASTRA University, University of Trans-Disciplinary Health Sciences and Technology, Manipal Academy of Higher Education, Foundation for Neglected Disease Research, University of North Carolina at Chapel Hill, Genentech, Virginia Commonwealth University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,500
Funders: Cystic Fibrosis Foundation, Children's Investment Fund Foundation, Chan Zuckerberg Initiative, Department of Biotechnology, Ministry of Science and Technology, India, Council of Scientific and Industrial Research, India, Science and Engineering Research Board, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G1917348475, G2820047379, G4867707873, Host microbiota and airway mucus: a novel paradigm for lung defense and immune homeostasis during early post-natal development, G631129105, G7837158021, G8008571369, G8997417011, Multi-Scale Investigations of Respiratory Mucus/Mucin Structure and Function in Health and Disease, UNC Cystic Fibrosis Research and Translation Core Center
OpenAlex ID: W7125521637