In a new preclinical study, researchers demonstrate that a pathway in the brain’s collection of blood vessels also supports neural circuits in the cerebellum that govern fine motor control. The findings expand current understanding of the role of the brain’s vasculature in neurodevelopment, and may have implications for future therapeutic research to treat disorders that affect motor control. The brain’s maze of blood vessels molds the development of the central nervous system, as it feeds neurons with oxygen and nutrients, removes wastes products, and offers a conduit for signaling molecules. Beyond these supportive roles, research also suggests that the vasculature itself can shape the activity of neural patterns in other regions of the brain. For example, recent work has suggested that endothelial cells found in these vessel networks directly act on nerve cells to influence their proliferation and maturation, as well as the plasticity of synapses. Now, Jinjin Lu and colleagues showcase a novel connection between the brain’s vasculature and the function of the cerebellum, the wrinkled structure at the base of the brain that controls fine movements. While studying male mice, they found that vascular endothelial cells harbored an enzyme named PRMT5 that indirectly controlled neural circuits in the cerebellum. Specifically, PRMT5 suppressed the expression of a vessel-remodeling factor named ANGPTL4 through an epigenetic mechanism. Furthermore, mice that lacked the gene Prmt5 had high levels of ANGPTL4, which broadcasted a deluge of inhibitory signals that suppressed synapse formation in the cerebellum and led to motor deficits. “Beyond its critical barrier and circulatory functions, the vasculature thus contributes molecular instructions that shape neural circuit connectivity,” Dario Bonanomi concludes in a related Focus, which also touches on future directions in the field.
Science Signaling
A PRMT5-ANGPTL4 axis in brain endothelial cells regulates cerebellar inhibitory synaptogenesis and motor coordination
20-Oct-2026