Researchers at the University of Exeter have created a detailed temporal map of chemical changes to DNA through development and aging of the human brain, offering new insights into how conditions such as autism and schizophrenia may arise.
The team studied epigenetic changes – chemical tags on our DNA that control how genes are switched on or off. These changes are crucial in regulating the expression of genes, guiding brain cells to develop and specialise correctly.
One important mechanism, called DNA methylation, was examined in nearly 1,000 donated human brains, spanning life from just six weeks after conception through to 108 years of age. The researchers focused on the cortex, a region of the brain involved in high-level functions such as thought, memory, perception, and behaviour. Correct development of the cortex during early life is important to support healthy brain function after birth.
The study, published today in Cell Genomics, revealed that DNA methylation changes dramatically before birth, reflecting the activation of key biological pathways needed to build the cortex. The researchers also discovered that neurons – the brain’s main signalling cells – start to show unique patterns of DNA methylation early in development, different from other brain cells.
Importantly, genes linked to autism and schizophrenia were found to undergo especially dynamic DNA methylation changes during brain development. This suggests they play a vital role during development of the brain’s cortex, and that disruptions to these processes could contribute to these conditions.
By analyzing how chemical changes to DNA shape the brain across the human lifespan, we’ve uncovered important clues about why neurodevelopmental conditions like autism and schizophrenia may develop. Our findings highlight that their roots may lie very early on in brain development.”
Alice Franklin, first author on the study, University of Exeter
The study confirms that epigenetic processes are essential for creating different brain cell types and may help explain how and why developmental differences occur.
Professor Jonathan Mill at the University of Exeter, who directed the research, added: “This work gives us a clearer picture of the biological processes guiding brain development and how these differ across cell types. In the long term, this could help us move closer to understanding the mechanisms underpinning neurodevelopmental conditions.”
The study was funded by the Simons Foundation Autism Research Initiative, the Medical Research Council and the European Union’s Horizon Programme. It was supported by Wellcome and the NIHR Exeter Biomedical Research Centre. The study is titled “Cell-type-specific DNA methylation dynamics in the prenatal and postnatal human cortex”, and is published in Cell Genomics.
Source:
Journal reference:
Franklin, A., et al. (2025). Cell-type-specific DNA methylation dynamics in the prenatal and postnatal human cortex. Cell Genomics. doi.org/10.1016/j.xgen.2025.101010