Primary cilium is a solitary, microtubule-based organelle that extends from the cellular membrane and is found in most mammalian cell types, including neurons and glial cells. This organelle serves as an antenna for signal transduction, hosting various receptors that transmit extracellular stimuli to intrinsic effectors, thereby supporting normal cellular function. Primary cilium plays a crucial role in mammalian neurodevelopment by regulating multiple pathways, including Sonic Hedgehog, Wnt, Notch, and TGFβ signaling. Disruption of primary cilium in neurons and glial cells impairs normal brain development. Our research group aims to investigate the functions of primary cilia in neurons and glial cells and elucidate the mechanisms underlying their roles in mammalian neurodevelopment. We employ human stem cell-derived co-culture and organoid models, coupled with cell biology, neurophysiology, and bioinformatics approaches to provide mechanistic insights.

Mutations in primary cilium-associated genes have been linked to neurodevelopmental disorders in humans. Our research group has used genome editing techniques to introduce specific mutations into human induced pluripotent stem cells (iPSCs). These mutant iPSCs are subsequently differentiated into neuronal models to assess the impact of ciliary dysfunction on neurodevelopment. Additionally, ciliary defects have been implicated in adult-onset neurodegenerative diseases. To further investigate the pathogenic role of primary cilium, we have obtained patient iPSCs, which are in turn differentiated into disease-relevant neuronal subtypes. These models allow us to dissect the mechanisms by which ciliary deficits contribute to disease pathogenesis. Our work aims to uncover the role of primary cilium in both neurodevelopmental and neurodegenerative disorders, providing a potential new target for disease-modifying therapy.

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