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

Often mouse models were adopted to recapitulate the ASD pathology, however, difficulties reside in distinguishing neural abnormalities primarily responsible for the autistic behavior. Chromatin remodeler, CHD8, is encoded by the most frequently mutated gene in individuals with ASD.

Here we investigated the etiology of the ASD due to CHD8 mutation by identifying the critical period to develop behavioral symptoms. By applying inducible Cre/loxP system and behavioral examinations, we discovered that neural stem cell-specific mutation of Chd8 at E14.5, but not at E17.5, manifested behavioral phenotypes. Single cell transcriptome analysis revealed that Chd8 mutation was associated with premature cell-cycle exit and differentiation at ventral progenitor cells.