COG5-mediated Golgi organization coordinates neural progenitor fate during human brain development

COG5 deficiency in human brain organoids disrupts Golgi organization and Golgi-to-ER retrograde trafficking, linked to reduced basal progenitor abundance and premature apical differentiation.

• Why it matters: The role of non-canonical Golgi architecture in human corticogenesis is unclear, and COG5-related glycosylation disorders offer a way to connect trafficking, membrane glycosylation, and lineage control.
• What they did: Using patient-derived fibroblasts and brain organoids, the study combined N-glycomics, glycolipidomics, single-cell transcriptomics, and trafficking and localization assays for cleaved Notch1 and ACBD3.
• The result: Organoids showed altered ventricular organization, rewired single-cell developmental trajectories with neuronal pathway activation, reduced Notch signalling, and altered cleavage plane orientation, implying Golgi architecture regulates apical radial glial fate.

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