GABA/Glutamate Neuron Differentiation Imbalance and Increased AKT/mTOR Signaling in CNTNAP2^-/- Cerebral Organoids.

ABSTRACT:

Background

The polygenic nature of autism spectrum disorder (ASD) requires the identification of converging genetic pathways during early development to elucidate its complexity and varied manifestations.

Methods

We developed a human cerebral organoid model from induced pluripotent stem cells with targeted genome editing to abolish protein expression of the CNTNAP2 ASD risk gene.

Results

CNTNAP2^-/- cerebral organoids displayed accelerated cell cycle, ventricular zone disorganization, and increased cortical folding. Proteomic analysis revealed disruptions in glutamatergic/GABAergic (gamma-aminobutyric acidergic) synaptic pathways and neurodevelopment, and transcriptomic analysis revealed differentially expressed genes belonging to inhibitory neuron-re

SUBMITTER: Chalkiadaki K 

PROVIDER: S-EPMC11699409 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature