Primary cilia in neural development and disease.

This research paper examines primary cilia - tiny structures found on most cells that act like cellular "antennas" for receiving and processing signals. Scientists used to think these structures weren't very important, but now understand they play a crucial role in brain development by helping coordinate multiple communication pathways that guide how the nervous system forms and functions. The researchers found that when primary cilia don't work properly, they can cause a wide range of brain-related conditions. This includes classic "ciliopathies" (diseases caused by faulty cilia) like Bardet-Biedl syndrome, Joubert syndrome, and Meckel-Gruber syndrome, but also potentially contributes to more complex conditions like autism, schizophrenia, and bipolar disorder. The paper suggests these conditions exist on a spectrum - some cause severe structural brain problems, while others lead to more subtle functional difficulties. While this research is still in early stages and focuses on understanding the basic science, the authors are optimistic about future treatments. They mention promising approaches like using lab-grown brain tissue models to study these conditions better, advanced imaging techniques to see cilia in more detail, and developing therapies specifically targeted at fixing ciliary problems. This could eventually lead to new treatment options for children with Bardet-Biedl syndrome and related conditions.

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.