How human-specific DNA changes shape brain development is poorly understood. Mosti et al. discover a human enhancer, HAR1984, which drives ETV5 and TRA2B expression via human-enriched chromatin interactions. ETV5-HAR1984 binding generates a positive regulatory feedback, promoting cortical neurogenesis across human and chimpanzee organoids and cortical size and folds in mice.

How human-specific DNA changes shape brain development is poorly understood. Mosti et al. discover a human enhancer, HAR1984, which drives ETV5 and TRA2B expression via human-enriched chromatin intera...

Humans exhibit significant phenotypic differences from other great apes, yet pinpointing the underlying genetic changes has been limited by incomplete reference genomes and a reliance on single assemb...

Finding adds to the bigger picture of how humans developed such large brains.

Author summary DDX3X mutations are associated with neurodevelopmental disorders, including DDX3X syndrome and autism spectrum disorder. DDX3X is an RNA binding protein whose loss of function impairs b...