Proximity labeling proteomics maps radial glial ciliary proteins across the developing telencephalon

Primary cilia in radial glia act as signaling hubs essential for brain development, yet their molecular roles remain poorly understood. Here, using proximity-labeling-mediated in vivo proteomics, we systematically mapped ciliary proteins in the developing telencephalon. Our dataset reveals region-specific ciliary composition across the dorsal and ventral telencephalon. We identified and validated ribosome proteins and translational machinery components in radial glial cilia. Further, we uncovered ciliary roles for neurodevelopmental disorder-associated proteins, including MARCKS, a key regulator of radial glial polarity, and CKAP2L, a protein linked to Filippi syndrome. Functional studies show that MARCKS contributes to ciliogenesis and CKAP2L regulates neurogenesis by modulating Hedgehog signaling. These findings highlight previously unrecognized mechanisms by which primary cilia modulate brain formation. Our in vivo ciliary proteomic dataset provides a unique resource for understanding ciliary functions in brain development and developmental disorders.