Primary cilia in neural development and disease

The Primary cilium, a non-motile organelle, was long underestimated but has recently been recognized as a pivotal signaling platform in nervous system development. This review summarizes the structural features, biogenesis, and dynamic regulation of primary cilia, and systematically examines their roles in neural stem cells fate determination, neurogenesis, neuronal migration, axon guidance, and synaptogenesis. By integrating multiple developmental signaling pathways, including Sonic hedgehog, Wnt, Notch, and mTOR, primary cilia orchestrate the precise spatiotemporal patterning of the nervous system. Dysfunction of primary cilia is closely linked to a wide spectrum of neurodevelopmental disorders, ranging from classical ciliopathies such as Meckel-Gruber syndrome, Joubert syndrome, and Bardet-Biedl syndrome, to complex conditions such as autism spectrum disorder, schizophrenia, and bipolar disorder, all of which can be traced to ciliary signaling imbalances. This paper introduces the concept of the continuous spectrum of Ciliogenesis, in which phenotypes from severe structural malformations to subtle functional abnormalities can be attributed to defects in specific ciliary modules. Future interventions, including organoid models, super-resolution imaging, and cilia-targeted therapeutic strategies, hold promise for advancing pathological insights and developing novel treatments for neurodevelopmental disorders.