The findings suggest that small genetic changes in DNA enhancers like HARE5 can substantially influence neural development, potentially offering insights into genetic factors related to neurodevelopmental disorders.

Future research may explore how similar DNA sequences impact neural function and cognitive development, particularly in relation to conditions such as autism spectrum disorder.

Located on chromosome 10, HARE5 enhances the expression of the FZD8 gene, which is vital for the WNT signaling pathway involved in cortical development.

A groundbreaking study published in Nature on May 20, 2025, by researchers at Duke University Medical Center has pinpointed a human-specific DNA enhancer known as HARE5, which plays a crucial role in regulating brain development.

The study revealed that HARE5 knock-in mice exhibited enhanced proliferation and self-renewal of radial glial cells during early development, suggesting an improved neurogenic potential.

These knock-in mice also demonstrated increased cortical size and a greater number of neurons compared to control groups, underscoring HARE5's significant role in neurodevelopment.

The research further identified mutations associated with autism spectrum disorder near Variant I, which significantly reduced enhancer activity and correlated with decreased neural progenitor proliferation.

Conversely, the absence of HARE5 was shown to lead to reduced cortical size in mouse models, emphasizing its necessity for proper cortical development.

Four specific nucleotide substitutions in HARE5 were identified as key drivers of increased enhancer activity, particularly Variants I and II, which accounted for about 80% of the observed effects.

To investigate these effects, mouse models expressing human, chimpanzee, or mouse versions of HARE5 were created for comparative analysis.