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

Area of Science:

• Neuroscience
• Cell Biology
• Developmental Biology

Background:

• Primary cilia in radial glia are crucial signaling hubs for brain development.
• The precise molecular functions of these cilia are not well understood.

Purpose of the Study:

• To systematically map proteins within primary cilia of radial glia in the developing telencephalon.
• To identify novel molecular mechanisms underlying cilia function in brain development and neurodevelopmental disorders.

Main Methods:

• Utilized proximity-labeling-mediated in vivo proteomics to identify ciliary proteins.
• Performed functional studies to investigate the roles of identified proteins.

Main Results:

• Revealed region-specific differences in ciliary protein composition between dorsal and ventral telencephalon.
• Identified ribosome proteins and translational machinery components within radial glial cilia.
• Uncovered roles for neurodevelopmental disorder-associated proteins, MARCKS and CKAP2L, in ciliogenesis, radial glia polarity, and neurogenesis via Hedgehog signaling modulation.

Conclusions:

• Primary cilia in radial glia possess previously unrecognized molecular machinery, including translational components.
• MARCKS and CKAP2L play significant roles in regulating neurogenesis and brain development.
• The generated proteomic dataset serves as a valuable resource for studying ciliary functions in development and disease.