Exploring Ciliary Mechanisms in the Causation of Hydrocephalus in Humans-Similarities and Differences from Animal Models

Hydrocephalus is a condition defined by excessive cerebrospinal fluid (CSF) relative to the brain volume. Congenital and infantile forms of hydrocephalus are both genetically and physiologically heterogenous. Among the candidate genes implicated in hydrocephalus, many are associated with cilia, a subcellular structure involved in CSF circulation and neurodevelopment. First, we provide an overview of 129 genes associated with human hydrocephalus and currently reported in the literature, categorized according to their possible involvement in ciliary structure, ciliary function, or cilia-mediated processes/signalling pathways. Intriguingly, there are large differences in the prevalence and manifestations of cilia-related hydrocephalus in humans as compared to rodents. Second, we address these differences by revisiting human and animal studies to outline potential cilia-related mechanisms and molecular signalling pathways contributing to hydrocephalus. We propose that our rapidly expanding understanding of cilia's role in CSF circulation and brain development will support a more precise characterization of hydrocephalus subtypes, ultimately guiding the development of more personalized treatment strategies.