biostudies-literatureUnknown5(1)Chalkiadaki K<h4>Background</h4>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.<h4>Methods</h4>We developed a human cerebral organoid model from induced pluripotent stem cells with targeted genome editing to abolish protein expression of the <i>CNTNAP2</i> ASD risk gene.<h4>Results</h4>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-reBiological psychiatry global open science100413https://www.ebi.ac.uk/biostudies/studies/S-EPMC11699409biostudies-literatureGABA/Glutamate Neuron Differentiation Imbalance and Increased AKT/mTOR Signaling in CNTNAP2^-/- Cerebral Organoids.PMC11699409Chalkiadaki KMoschovas DZafeiri MAvgeropoulos AMason JOTypou ATheodoridou NSamiotaki MVoudouri GGkogkas CGStatoulla EAmvrosiadis TfalseGABA/Glutamate Neuron Differentiation Imbalance and Increased AKT/mTOR Signaling in CNTNAP2^-/- Cerebral Organoids.<h4>Background</h4>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.<h4>Methods</h4>We developed a human cerebral organoid model from induced pluripotent stem cells with targeted genome editing to abolish protein expression of the <i>CNTNAP2</i> ASD risk gene.<h4>Results</h4>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-re2025-01-01T00:00:00Z2025 Jan2026-06-01T23:12:46.174Z2026-05-23T03:08:04.582ZS-EPMC116994093975860410.1016/j.bpsgos.2024.100413