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Unveiling the Secrets of Brain Folding

New research sheds light on how the brain is folded during development and how its disruption can predispose risk for neurodevelopmental disorders such as epilepsy and autism.

By Marianne Lie Becker, , 6/6/2024

A recent study from the University of Southern Denmark has uncovered fundamental mechanisms behind the folding of the brain's cortex.

The research, led by Professor Vijay Tiwari from the Department of Molecular Medicine and published in Science Advances, provides new insights into brain development and neurological disorders such as epilepsy and autism.

What is the cortex?

The folding of the cortex, the outermost part of the brain, plays a central role in the development and evolution of the brain in mammals. The cortex is the largest part of the brain, and its folded appearance comes from folds called gyri and grooves called sulci.

These folding patterns are crucial for brain function and arise during fetal development. This folding allows for a massive expansion of the cortex's surface area while still fitting within a limited cranial volume.

-The folding also brings functionally related and highly connected areas of the cortex closer together. Therefore, it is crucial for higher cognitive functions, explains Vijay Tiwari.

-Errors in the development of the brain's folding patterns in humans can lead to significant learning disabilities and other cognitive problems.

The folding occurs in very specific patterns that are established early in brain development. These patterns are determined by a kind of genetic "map" called a transcriptomic protomap found in the early development zones of the cortex. When these patterns are disrupted, it can lead to neurological disorders.

Groundbreaking discoveries

Understanding the cellular and genetic mechanisms behind the folding of the brain's cortex in humans and other large mammals has been limited by the lack of suitable animal models. In recent years, the ferret has become an important model to fill this gap.

Researchers examined gene expression (which genes are active) and the epigenetic landscape (chemical changes that affect gene activity) in different parts of the brains of ferret fetuses where future folds and grooves would form. By analysing these factors, researchers discovered how the brain's complex folding patterns are formed.

The results showed that this genetic map begins to form very early in fetal development and involves signalling pathways that determine cell fate, i.e., what type of cells they will become.

Implications for the future

-We have developed a detailed map of gene expression in the folding brain, opening new avenues for future research and potential treatments, says Professor Vijay Tiwari.

-Our research offers hope for families affected by neurological disorders as it may lead to new treatment methods.

The findings improve our understanding of brain development and point to new targets for the treatment of neurological disorders.

Meet the researcher

The research project is led by Vijay Tiwari, Professor and Head of Research at the Genome Biology Research Unit at the Department of Molecular Medicine.



Gene expression: The process by which a gene gets turned on in a cell to make RNA and subsequently proteins.

Epigenetics: Chemical changes that affect gene activity without changing the DNA sequence.

Read the scientific article here.

Editing was completed: 06.06.2024