A tiny and largely overlooked structure inside human cells may hold important clues to how the brain develops, potentially opening new pathways for understanding developmental disorders and future treatments.
In a study published in the journal Cell Reports, researchers led by Xuecai Ge at the University of California, Riverside, investigated the primary cilium, a microscopic, antenna-like structure found on nearly every cell in the body. Although the structure is widespread, scientists have historically paid relatively little attention to it. “Even many biologists aren’t familiar with it,” said Ge, an associate professor of biomedical sciences in the university’s School of Medicine. “We still have a lot to learn about this organelle.”
For many years, researchers believed the primary cilium was little more than an evolutionary remnant with limited biological importance. More recent evidence, however, has suggested the opposite. Disruptions to the structure have been linked to ciliopathies, a group of disorders that can affect several organs, including the brain. “Patients may have kidney problems or obesity,” Ge explained, “but when you look at their brain structure, you often see abnormalities. That made us wonder if the cilium had a role to play in brain development.”
To investigate further, the research team examined neural progenitor cells, early-stage cells that eventually develop into neurons. Each of these cells contains a single primary cilium extending into the ventricles, the fluid-filled spaces within the developing brain. Using a large-scale biochemical analysis involving more than 1,000 mouse embryonic brains, the researchers identified the proteins present within these cilia, uncovering findings that challenged long-standing scientific assumptions.
“We discovered many proteins that no one expected to find in the cilium,” Ge said. “And in some cases, these proteins are directly linked to human developmental disorders.” One of those proteins, CKAP2L, is associated with Filippi syndrome, a condition linked to reduced brain size. When researchers removed the protein in mice, the animals developed smaller brains, suggesting the protein plays an important role in brain growth and development.
The study also revealed that primary cilia are not identical throughout the brain. Instead, their composition appears to vary depending on the brain region. “We identified over 40 proteins that vary between brain regions,” Ge said. “That suggests the cilium has specialized roles, not just a single uniform function.” The team also uncovered evidence suggesting that proteins may actually be produced inside the cilium itself, challenging the long-held assumption that proteins are manufactured elsewhere in the cell before being transported into the structure.
“The field has assumed that all proteins are made elsewhere in the cell and then transported into the cilium,” Ge said. “But we found the machinery that could make proteins on-site. It’s like finding a bread maker where you thought bread could only be delivered.” Although further research is needed to confirm whether this machinery is fully active, the discovery could reshape scientists’ understanding of cellular biology and help explain diseases affecting vision, organ function, and brain development. Looking ahead, Ge’s team plans to continue exploring how this tiny cellular structure shapes the developing brain. “We’ve only scratched the surface,” she said. “There’s a lot more to learn.”
More information: Xiaoliang Liu et al, Proximity labeling proteomics maps radial glial ciliary proteins across the developing telencephalon, Cell Reports. DOI: 10.1016/j.celrep.2026.117355
Journal information: Cell Reports Provided by University of California – Riverside
