Journal Article

Defective ventral neurogenesis due to midfetal Chd8 mutation drives autistic-like behavior in mice

Terakawa, Jumpei, Daikoku, Takiko, Higashi, Koichi, Kato, Kiyoko, Iwasaki, Tomoya, Horike, Shin-Ichi, Nishiyama, Masaaki, Kawamura, Atsuki, Nitahara, Kenta, Tashiro, Ayumu, Kurokawa, Ken

2026

Overview

Autism spectrum disorder (ASD) is a common neurodevelopmental condition characterized by behavioral abnormalities. Although mouse models have been widely adopted to recapitulate the pathology of ASD, the identification of specific neural abnormalities responsible for autistic-like behavior has remained challenging. Here we provide insight into this causal relation by identifying the critical period and cell type responsible for the development of such behavior in ASD model mice with a Chd8 mutation. We find that Chd8 mutation induced at embryonic day 14.5 gives rise to ASD-like behavioral phenotypes, including abnormal social interaction and increased anxiety-like behavior, as well as to accelerated cell-cycle exit and differentiation in ventral progenitor cells. Restoration of Chd8 expression in ventral progenitor cells ameliorates both the behavioral phenotypes and aberrant ventral differentiation in Chd8 mutant mice. Our findings indicate that Chd8 mutation during the midfetal period—in particular, in ventral progenitor cells—contributes to the development of autistic-like behavior. Midfetal Chd8 mutation in ventral progenitor cells disrupts neurogenesis, leading to altered neuronal development and autistic-like behaviors in mice. Restoring Chd8 in these cells rescues both neural defects and behavior.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/1 / 13/31 / 13/51 / 14/19 / 45/41 / 49/90 / 49/91 / 631/136/1425 / 631/378/1689/1373 / 631/378/2584/2585 / 64/60 / Abnormalities / Animal models / Animals / Anxiety / Autism / Autism Spectrum Disorder - genetics / Autistic Disorder - genetics / Behavior / Behavior, Animal / Cell differentiation / Cell Differentiation - genetics / Cells (biology) / Cesarean section / Differentiation / Disease Models, Animal / DNA-Binding Proteins - genetics / DNA-Binding Proteins - metabolism / Female / Gene expression / Genotype & phenotype / Humanities and Social Sciences / Male / Mice / Mice, Inbred C57BL / multidisciplinary / Mutation / Neural stem cells / Neurogenesis / Neurogenesis - genetics / Phenotypes / Postpartum period / Progenitor cells / Science / Science (multidisciplinary) / Social behavior / Stem cells / Stem Cells - metabolism / Transcription Factors - genetics / Transcription Factors - metabolism