GTF2I dosage regulates neuronal differentiation and social behavior in 7q11.23 neurodevelopmental disorders.

ABSTRACT: Copy number variations at 7q11.23 cause neurodevelopmental disorders with shared and opposite manifestations. Deletion causes Williams-Beuren syndrome featuring hypersociability, while duplication causes 7q11.23 microduplication syndrome (7Dup), frequently exhibiting autism spectrum disorder (ASD). Converging evidence indicates GTF2I as key mediator of the cognitive-behavioral phenotypes, yet its role in cortical development and behavioral hallmarks remains largely unknown. We integrated proteomic and transcriptomic profiling of patient-derived cortical organoids, including longitudinally at single-cell resolution, to dissect 7q11.23 dosage-dependent and GTF2I-specific disease mechanisms. We observed dosage-dependent impaired dynamics of neural progenitor proliferation, trans

SUBMITTER: Lopez-Tobon A 

PROVIDER: S-EPMC10686562 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature