Folding of the cerebral cortex—identification of important neurons

October 5, 2017, Kanazawa University
Folding of the cerebral cortex -- identification of important neurons
The ferret brain has the gyrus, i.e., folds, like the human brain. Credit: Kanazawa University

Folds in the cerebral cortex in mammals are believed to be indispensable for higher brain functions, but the mechanisms underlying cortical folding remain unknown. By using the latest genome editing tools, researchers have discovered neurons important for fold formation and the importance of the Cdk5 gene in those neurons. Lissencephaly is a condition in which cortical fold formation is impaired. The study may provide clues to diseases including lissencephaly.

The human brain is highly developed and higher functioning compared to other animals. One of the important factors contributing to the development of the brain is the gyrus, the fold on the surface. The cerebral cortex of higher animals, including humans, has many folds, called gyri. By acquiring these folds in the process of evolution, the human brain developed a larger number of , and thus great development of brain functions. On the other hand, the mouse, a widely used model animal, has a brain without gyri. This has made it very difficult to do research on the gyrus using the mouse as a model animal, which has inhibited research efforts.

The current study used ferrets, which have gyri similar to the human brain (Figure 1). The research group developed a technique for ferrets reported in several articles that allows analysis of ferrets at the genome level. By using this technique, the researchers developed a ferret disease model that shows impairment in the gyrus, which significantly contributes to new genetic approaches to the brains of higher mammals.

Folding of the cerebral cortex -- identification of important neurons
A tissue section of the ferret gyrus dyed in blue. Left: A cross section of a normal gyrus. The gyrus is protruding (arrowhead). Right: A cross section of a gyrus where Cdk5 is knocked out. The gyrus protrusion is much less obvious, which indicates that the Cdk5 function is important in the gyrus formation. Credit: Kanazawa University


By using the latest genome editing tool, a type of genetic engineering, the researchers knocked out a specific gene in the ferret cerebral cortex and elucidated one of the mechanisms of gyrus formation. They combined CRISPR/Cas9, the latest genome editing tool, to introduce a gene into the ferret cerebral cortex. This new technique opens a way to a new stage of genetics research of the of higher mammals.

Schematic illustration of cross section of the cerebral cortex. Dark blue, the surface side, i.e., the upper-layer, of the cerebral cortex; light blue, the deep side. Yellow triangles represent neurons. Before the gyrus formation, the number of neurons on the surface side is not big (left, neurons in the dark blue part), but it grows bigger with time (right, neurons in the dark blue part); this development is considered to be linked to the folding (gyrus formation) of the cerebral cortex. Cdk5 is an important genome for transportation of neurons to the brain surface. Credit: Kanazawa University

This procedure knocked out a gene called Cdk5 in the ferret cerebral cortex and which resulted in impaired gyrus formation (Figure 2). This result indicates that Cdk5 is an important gene for gyrus formation. The researchers then searched for neurons playing important roles in gyrus formation and found that neurons on the upper-layer cerebral cortex were essential (Figure 3). These results indicate that functions of Cdk5 in neurons of the upper-layer cerebral are important for the formation of the gyrus (Figure 3).

It is expected that this study will advance knowledge of evolution, which was previously quite difficult using a mouse model. Additionally, humans can develop rare diseases due to gyrus impairment, the pathogenesis of which is largely unknown. The new technique could elucidate the etiology of such diseases.

Explore further: Researchers develop new animal model to study rare brain disease

More information: Yohei Shinmyo et al, Folding of the Cerebral Cortex Requires Cdk5 in Upper-Layer Neurons in Gyrencephalic Mammals, Cell Reports (2017). DOI: 10.1016/j.celrep.2017.08.024

Related Stories

Researchers develop new animal model to study rare brain disease

March 17, 2017
Thanatophoric dysplasia (TD) is an intractable disease causing abnormalities of bones and the brain. In a recent study of ferrets, which have brains similar to those of humans, researchers using a newly developed technique ...

CD38 gene is identified to be important in postnatal development of the cerebral cortex

April 7, 2017
The brain consists of neurons and glial cells. The developmental abnormality of glial cells causes various diseases and aberrant cerebral cortex development. CD38 gene knockout is shown to cause aberrant development of glial ...

The formation of folds on the surface of the brain

May 5, 2017
Folds in the human brain enlarge the surface of this important processing organ and in this way create more space for higher functions including thought and action. However, certain species of mammals exist whose brains have ...

Brain plasticity: How adult-born neurons get wired-in

February 2, 2017
One goal in neurobiology is to understand how the flow of electrical signals through brain circuits gives rise to perception, action, thought, learning and memories.

Researchers discover an essential genetic mechanism of cerebral cortex development

September 19, 2013
The cerebral cortex is the most complex and vital structure in our brain. It is the nerve centre for those "higher" functions that characterise our species, such as language and abstract thought. The nerve cells – or neurons ...

Two heads are better than one: Gene expression reveals molecular mechanisms underlying evolution of cerebral cortex

November 9, 2012
Dramatic expansion of the human cerebral cortex, over the course of evolution, accommodated new areas for specialized cognitive function, including language. Understanding the genetic mechanisms underlying these changes, ...

Recommended for you

Study of protein 'trafficker' provides insight into autism and other brain disorders

September 22, 2018
In the brain, as in business, connections are everything. To maintain cellular associates, the outer surface of a neuron, its membrane, must express particular proteins—proverbial hands that reach out and greet nearby cells. ...

Breast milk may be best for premature babies' brain development

September 21, 2018
Babies born before their due date show better brain development when fed breast milk rather than formula, a study has found.

Early warning sign of psychosis detected

September 21, 2018
Brains of people at risk of psychosis exhibit a pattern that can help predict whether they will go on to develop full-fledged schizophrenia, a new Yale-led study shows. The findings could help doctors begin early intervention ...

White matter repair and traumatic brain injury

September 20, 2018
Traumatic brain injury (TBI) is a leading cause of death and disability in the U.S., contributing to about 30 percent of all injury deaths, according to the CDC. TBI causes damage to both white and gray matter in the brain, ...

Gut branches of vagus nerve essential components of brain's reward and motivation system

September 20, 2018
A novel gut-to-brain neural circuit establishes the vagus nerve as an essential component of the brain system that regulates reward and motivation, according to research conducted at the Icahn School of Medicine at Mount ...

Genomic dark matter activity connects Parkinson's and psychiatric diseases

September 20, 2018
Dopamine neurons are located in the midbrain, but their tendril-like axons can branch far into the higher cortical areas, influencing how we move and how we feel. New genetic evidence has revealed that these specialized cells ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.