# Nephronophthisis-related ciliopathies and ciliary specialization > **NIH NIH R01** · RUTGERS, THE STATE UNIV OF N.J. · 2024 · $554,838 ## Abstract Project Summary Cilia play essential roles in human development and health. Ciliary ubiquity and diversity are reflected in multi-symptom ciliopathies caused by ciliary defects. The clinical severity of ciliopathy gene mutations varies between cell types and includes cystic kidney disease, neurological and skeletal defects, retinal degeneration, situs inversus, and male infertility. While the same basic intraflagellar transport (IFT) machinery constructs all cilia and flagella, the mechanisms underlying ciliary specialization are poorly understood. For example, cilia produce extracellular vesicles (EVs). Whether EV shedding is a general property of cilia or a specialized feature of some cilia types is unknown. The functions of ciliary EVs and their contributions to ciliopathies are also poorly understood. The long-term goal of this project is to identify molecular mechanisms regulating ciliary specialization, remodeling, plasticity, EV biogenesis, and EV functions. Cilia of the C. elegans inner labial-type 2 (IL2) neurons display several specializations: they have unique microtubule ultrastructure, specialized IFT, and shed EVs. The IL2 ciliary transition zone (TZ) and axoneme is structurally plastic and remodels from one structure to another during animal development: from a canonical 9+0 to non-canonical 6+0 structure. While cilia and flagella share a 9-fold microtubule doublet symmetry, variations in microtubule numbers are observed in nature. Renal primary cilia do not conform to the 9 + 0 paradigm. This developmental plasticity suggests that some ciliary defects (ciliopathies) may be corrected at later times. Our hypothesis is supported by the recent discovery that autosomal dominant polycystic kidney disease is reversible, and that the kidney displays structural plasticity. Our simple C. elegans model allows us to uncover mechanisms that regulate ciliary remodeling and plasticity. We found that TZ remodeling requires IFT and the tubulin code – combinatorial use of tubulin isotypes, glutamylation, and microtubule-associated proteins. Nephronophthisis-related ciliopathies (NPHP-RCs) are associated with defects in TZ-associated proteins. NPHP-RCs include nephronophthisis, Meckel Gruber (MKS), Joubert (JBTS), and Senior-Løken syndromes. The clinical severity of loss of function of NPHP-RC genes varies between cell and cilia types, thus it is imperative to understand ciliary and EV biology in a variety of contexts. We will use C. elegans to identify mechanisms driving transition zone and axonemal remodeling and plasticity in non-canonical primary cilia. Ciliary EV shedding is a conserved, yet little is known about how and why cilia make EVs. We will test the hypotheses that ciliary remodeling and a non-canonical structure impacts EV biogenesis and EV function. ## Key facts - **NIH application ID:** 10774295 - **Project number:** 5R01DK116606-06 - **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J. - **Principal Investigator:** Maureen M Barr - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $554,838 - **Award type:** 5 - **Project period:** 2023-02-15 → 2026-12-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10774295 ## Citation > US National Institutes of Health, RePORTER application 10774295, Nephronophthisis-related ciliopathies and ciliary specialization (5R01DK116606-06). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10774295. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*