Beneath the surface of the tiny, see-through worm Caenorhabditis elegans, researchers have found new clues about how certain hair-like structures on cells, called cilia—tiny projections that help cells sense their surroundings and move materials—grow in a synchronized way. These structures help the worm detect its environment and often grow next to each other in matching pairs. Until now, how these pairs stay aligned as they grow has been a mystery. Scientists have now learned that a protein known as ARL13B, which is involved in organizing and signaling these structures, plays a key role in managing this side-by-side growth, a pattern they describe as “juxtaposed cilia-cilia elongation”—meaning two neighboring cilia grow in step with each other.
Based at Abdullah Gul University, researchers Merve Gul Turan, Hanife Kantarci, Dr. Sebiha Cevik, and Dr. Oktay Kaplan explored this phenomenon and how ARL13B, together with other molecules, supports the coordinated growth of cilia. Their results were published in the journal iScience.
Looking closely using special glowing markers under the microscope—a tool that uses fluorescent light to highlight specific parts of cells—the scientists tracked how some of the worm’s sensory nerve cells grow their cilia in matching pairs. In the worm’s head, these projections stretch side by side, and in the tail, they form Y-shaped structures. Even though the actual length of each cilium could vary, the pattern of paired growth stayed the same. However, when the ARL13B protein was missing, the cilia no longer met up properly and, in many cases, pointed in different directions.
Curiously, this misalignment happened even though the cilia stayed about the same length as in worms with normal ARL13B. This finding shows that the protein’s role isn’t just about how long cilia grow but also about helping them stay in step. “Our genetic analyses reveal that ARL-13 affects juxtaposed cilia-cilia elongation independently of cilia length,” Dr. Kaplan said.
The scientists also found that interrupting a group of helper proteins called the Bardet-Biedl syndrome protein complex—a collection of proteins that assist with transporting materials inside cilia—could actually improve the alignment issue in worms lacking ARL13B. This points to a possible link between ARL13B’s job and changes in the outer layer of the cilia, known as the ciliary membrane, which acts like a skin around the structure. “We propose that ARL-13 contributes to juxtaposed cilia-cilia elongation, partly through the modulation of the ciliary membrane,” Dr. Cevik explained.
Introducing the ARL13B protein back into the worms restored proper alignment of the cilia pairs. This confirmed the importance of this single protein in keeping the cilia coordinated. The team also tested other genes known to affect how long cilia grow, such as cyclin-dependent kinase-like 1—a gene involved in regulating cell activity—and defective dye filling protein 5, which plays a role in building cilia. These genes, however, had no impact on the alignment issue, suggesting that different biological pathways control cilia length and side-by-side growth.
Some combinations of gene changes caused even more noticeable problems. Removing both ARL13B and another gene, nephronophthisis 2—a gene linked to kidney disease that also affects cilia—made the alignment worse. When a third gene, histone deacetylase 6, which helps regulate proteins and cell structure, was also removed, the cilia became longer but still failed to align. These results suggest that ARL13B is part of a broader network of proteins that help maintain the proper layout of cilia.
To understand more about the role of the outer surface of cilia, scientists looked at a specific fat-like substance called a lipid marker, which usually stays outside the cilia. In the absence of ARL13B, this substance showed up inside the cilia, signaling a shift in the membrane’s behavior. When the Bardet-Biedl syndrome protein complex was removed in these mutants, this lipid returned to its usual location, supporting the idea that ARL13B helps manage the cilia membrane.
Dr. Kaplan and his colleague’s findings provide strong support for the idea that ARL13B helps organize cilia through changes in the cilia’s surface, not just its inner structure. Dr. Kaplan believes that other sticky molecules, known as adhesion molecules, which help cells attach to each other, might also help maintain the close bond between these paired cilia and should be explored in future studies.
Journal Reference
Turan M.G., Kantarci H., Cevik S., Kaplan O.I. “ARL13B regulates juxtaposed cilia-cilia elongation in Bardet-Biedl syndrome protein complex dependent manner in Caenorhabditis elegans.” iScience, 2025. DOI: https://doi.org/10.1016/j.isci.2025.111791
About the Authors
Dr. Sebiha Cevik is a molecular biologist and a leading researcher at Abdullah Gul University, Turkey, where she focuses on the cellular mechanisms behind rare genetic disorders. Her work explores how cellular structures like cilia contribute to human health and development, with particular attention to their roles in sensory function and disease. Dr. Cevik has authored several influential studies in the field and actively mentors young scientists in biomedical research.
Dr. Oktay Kaplan is a geneticist at Abdullah Gul University known for his work on cilia biology and cellular organization. His research investigates how molecular signals coordinate the development and structure of microscopic cell projections, advancing our understanding of genetic diseases linked to cilia dysfunction. Dr. Kaplan is also recognized for building innovative imaging and genetic tools to study live model organisms such as Caenorhabditis elegans.
