Human-specific DNA Enhancer Influences Brain Development and Neuronal Growth

Recent research led by Duke University Medical Center highlights the role of a unique human-specific DNA enhancer in shaping brain development, particularly in the proliferation of neural progenitor cells and the expansion of the cerebral cortex. This enhancer, known as HARE5 and located on chromosome 10, acts as a regulatory element for the FZD8 gene, which is integral to the WNT signaling pathway involved in neural growth.

Genetic modifications in HARE5 have been shown to amplify developmental pathways, leading to increased cortical size and a greater number of neurons in experimental models. The study utilized advanced genome editing techniques, including CRISPR interference and single-cell RNA sequencing, to assess how nucleotide variations in HARE5 influence neural progenitor activity and corticogenesis.

In genetically engineered mouse models with human, chimpanzee, or mouse versions of HARE5, researchers observed that the human-specific enhancer variants significantly enhanced cortical growth. Humanized mice exhibited larger brain cortices and a higher count of mature neurons, especially in the upper layers of the cortex. Further analyses demonstrated that four specific human nucleotide substitutions in HARE5 collectively boost enhancer activity, with variants I and II contributing most significantly.

Functional experiments revealed that mutations associated with autism spectrum disorder could diminish the enhancer’s activity and reduce neural proliferation. Conversely, knockout models confirmed HARE5’s essential role in cortical expansion. These findings suggest that small genetic changes in non-coding DNA sequences can have profound impacts on brain structure and function.

This research offers valuable insights into the genetic mechanisms underpinning human brain evolution and opens avenues for understanding neurodevelopmental disorders. The identification of regulatory DNA elements like HARE5 emphasizes the complex interplay between genetics and brain development, shedding light on how evolutionary modifications contribute to advanced cognitive capabilities.

Future studies aim to explore how similar regulatory sequences influence neural cognition and their potential links to disorders such as autism, advancing our understanding of human brain uniqueness and its vulnerabilities.

Source: https://medicalxpress.com/news/2025-05-human-specific-dna-linked-brain.html