Image: Oier Pastor-Alonso/UCSF
A new study has provided an unprecedented look at how gene regulation evolves during human brain development, showing how the 3D structure of chromatin – DNA and proteins – plays a critical role. This work offers new insights into how early brain development shapes lifelong mental health.
The study was a collaboration between scientists at the Salk Institute, UC Los Angeles, UC San Francisco, UC San Diego, and Seoul National University. The team created the first map of DNA modification in the hippocampus and prefrontal cortex – two regions of the brain critical to learning, memory, and emotional regulation. These areas are also frequently involved in disorders like autism and schizophrenia.
“Growing a healthy human brain is a tremendous feat,” says study co-author Joseph Ecker, Salk professor. “Our study establishes an important database that captures key epigenetic changes that occur during brain development, in turn bringing us closer to understanding where and when failures arise in this development that can lead to neurodevelopmental disorders like autism.”
The research team analyzed more than 53,000 brain cells from donors spanning mid-gestation to adulthood, revealing significant changes in gene regulation during critical developmental windows. In capturing such a broad spectrum of developmental phases, the researchers were able to assemble a remarkably comprehensive picture of the massive genetic rewiring that occurs during critical timepoints in human brain development.
“Our study tackles the complex relationship between DNA organization and gene expression in developing human brains at ages typically not interrogated: the third trimester and infancy,” says study co-lead author Mercedes Paredes, an associate professor of neurology at UCSF. “The connections we’ve identified across different cell types through this work could untangle the current challenges in identifying meaningful genetic risk factors for neurodevelopmental and neuropsychiatric conditions.”
Source: UCLA Newsroom
Image: Oier Pastor-Alonso/UCSF