Yuqing Xiang

One of the most basic principles in embryonic development is ensuring the proper size of tissues and organs to meet functional needs. So far, an endogenous metabolite regulating organ size has not been described. The current study highlights itaconate, the product of Irg1, in regulating zebrafish neuromast size. Single-cell transcriptomic sequencing analysis of enzymes catalyzing metabolic processes revealed that irg1l, a homolog of Irg1, is highly expressed in supporting cells of developing neuromast in zebrafish. Deficiency of irg1l reduced the size of the neuromast and caused auditory dysfunction. Conversely, overexpression of irg1l resulted in increased size due to excessive proliferation of supporting cells. Notably, 4-octyl itaconate (4-OI), an itaconate derivative, treatment recapitulates the phenotype of irg1l overexpression and increases the neuromast size. Finally, we revealed that the Irg1l/itaconate axis induces metabolic reprogramming to promote activation of the Yap, drive supporting cell proliferation, and enlarge neuromast size. These findings provide a novel insight into the role of metabolites in organ development.

Brain endothelial cells (BECs) constitute the core component of the blood–brain barrier (BBB), regulating substance exchange between blood and the brain parenchyma to maintain central nervous system homeostasis. In pathological states, the BBB exhibits the disruption of tight junctions, endothelial cell (EC) damage, and increased permeability, accompanied by neuroinflammation, oxidative stress, and abnormal molecular signaling pathways, leading to neurotoxic effects in the brain parenchyma and exacerbating neurodegeneration and disease progression. This review systematically summarizes the developmental origin, structural characteristics, and pathological mechanisms of BECs in diseases such as Alzheimer’s disease, multiple sclerosis, stroke, and glioblastoma with a particular focus on the regulatory mechanisms of the Wnt/β-catenin and VEGF signaling pathways. By integrating the latest research advances, this review aims to provide a comprehensive perspective for understanding the role of BECs in physiological and pathological states and to provide a theoretical basis for the development of BBB-based therapeutic approaches for neurological diseases.