DNA from embryonic brain provides insight into psychiatric disorders

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2 May 2024

The embryonic brain has never been mapped before. But now Marijn Schipper and Danielle Posthuma of the Vrije Universiteit Amsterdam and Camiel Mannens and Stin Linnarsson of the Karolinksa Institutet in Sweden have created a large atlas of half a million cells in the embryonic brain. They also mapped out which pieces of DNA are 'open' and therefore active in these cells. This new atlas ensures that the development of different types of cells in healthy brains can be better studied.

By understanding what healthy development of the different types of brain cells looks like, researchers can also better understand how disruptions to these cells can lead to diseases. This can be read in the research published in Nature.

Active DNA
Similar atlases have been made before in humans, but never before in the entire brain during early embryonic development. "The early embryonic stage is a crucial period in brain development. Many cells specialise and this involves a very precise organisation of the DNA. During this period, some pieces of DNA are closed, they have no function in that cell at that moment, and some pieces of DNA are open. In that cell, these pieces of DNA play an important role in regulating the expression of proteins," explains neuroscientist Danielle Posthuma.

Detecting errors at an early stage
Different cell types, for example neurons, can be characterised by the patterns of the stretches of DNA that are open and closed. These patterns therefore also change over time. The researchers deliberately chose to map the open stretches of DNA in early embryonic development because errors at this early stage can have major consequences, for example for the development of psychiatric disorders.

Development of psychiatric disorders
For example, Marijn Schipper has investigated whether the pieces of DNA that are active in specific cell types contain genetic variants, which are known from previous large-scale genetic patient research to be involved in the development of psychiatric disorders. The analyses showed that the patterns of the open pieces of DNA coincide with pieces of DNA that are also linked to ADHD, anorexia, autism spectrum disorders, depression, insomnia and schizophrenia.

Depression
The strongest association was found for depression. For example, the researchers discovered that genetic variants that have previously been linked to depression are particularly common in stretches of DNA that are mainly active during early embryonic development in a specific type of neurons in the midbrain. This link with the midbrain is new, and offers new research directions with a specific focus on the midbrain for understanding the hereditary component of depression.

More targeted research
The new atlas offers a wealth of information about how the early embryonic brain develops and how the regulation of DNA in different cell types plays a role in this. This information also provides greater insight into processes when things go wrong, such as in psychiatric disorders but also in the development of different types of brain tumours.