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Targeting Notch signaling to restore neural development and behavior in mouse models of ASD [RNAseq_embryo_hanno]

GSE293282 Mus musculus Expression profiling by high throughput sequencing 9 samples Submitted 2026/01/26 Platform GPL24247
Summary
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with diverse genetic and environmental origins, yet whether these factors converge on common molecular pathways remains unclear. This study identifies dysregulation of the Notch signaling pathway as a shared mechanism in both hereditary and nonhereditary ASD models. Aberrant histone deacetylase 3-mediated epigenetic regulation of Notch signaling during embryonic forebrain development disrupts the specification of caudal ganglionic eminence (CGE) progenitors into vasoactive intestinal peptide (VIP+) GABAergic interneuron subtypes (VIP-INs). CGE-specific ablation of Notch1/2 genes in ASD models restores the loss of VIP-INs, normalizes maladaptive excitatory and inhibitory balance, and selectively improves social behaviors. Remarkably, a single antenatal dose of a γ-secretase inhibitor ameliorates multiple ASD-associated neuronal, behavioral, and transcriptomic changes in adult models. The study indicates a strong convergence of ASD-related factors on Notch signaling dysregulation and establishes this pathway as a promising therapeutic target for developmental and behavioral deficits in ASD.
Published in
Targeting notch signaling to restore neural development and behavior in mouse models of ASD
Hanno Y, Nakanishi M, Takase A et al. · Nature communications 2026 · PMID 41912527 · doi:10.1038/s41467-026-70321-6
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Also filed as BioProject PRJNA1243699 and SRA study SRP574107. Searching any of these in the dataset finder brings you back here.

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