Fold formation of the cerebral cortex requires FGF signaling in the mammalian brain

December 13, 2017, Kanazawa University
Fold formation of the cerebral cortex requires FGF signaling in the mammalian brain
Left: Schematic picture of the brain, a side view. Right: Schematic picture of the brain, a sectional view. Credit: Kanazawa University

The cerebral cortex is particularly important in higher brain functions. The cerebral cortex of higher animals, including humans, has many folds, called the gyrus (Figure 1). Because of the gyrus, higher animals have a large number of neurons, 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; therefore, research on the gyrus has been much retarded.

A research group at Kanazawa University, Japan, has been using the ferret, a higher mammal, that has a brain more similar to the human brain than that of the mouse. The ferret brain is known to have gyri, but researchers lack techniques for ferret brain studies. The research group developed a technique for the ferret brain, which allows analysis of ferrets at the genome level, and reported the results in 2012 and 2013. By using this technique, they succeeded in developing a ferret disease model that shows impairment in gyrus formation. In the present study, using their technique, they have identified a signaling pathway that plays important roles in gyrus formation in the cerebral of higher mammals.

Fold formation of the cerebral cortex requires FGF signaling in the mammalian brain
Side views of the ferret brain. In each view, right and left correspond to the anterior and posterior sides. In a normal ferret brain, a gyrus extends in a straight manner (arrow head), while in an abnormal ferret brain where FGF signaling is inhibited, a gyrus is discontinued (arrow). This result shows the importance of FGF signaling in gyrus formation. The bright area in the right lower panel indicates the position where FGF signaling is inhibited. Credit: Kanazawa University

The Kanazawa University group has investigated mechanisms involved in gyrus formation during early ferret cerebral cortex development, and identified for the first time that FGF signaling) is important in gyrus formation.

Major findings of the study include:

  1. Expression of FGF receptors is augmented where gyrus formation is about to take place. Examination of tissue sections of various cerebral cortex regions that express FGF receptors indicated that regions destined to form gyri expressed more FGF receptors than other regions. This result suggests the possibility that FGF receptors mediate gyrus formation.
  2. When FGF signaling is inhibited, gyrus formation is impaired. In order to verify the above possibility, FGF signaling in the ferret brain was inhibited by using the technique previously developed by the research group. As expected, gyrus formation was impaired (Figure 2). This result indicates that FGF signaling is important for gyrus formation.
  3. Inhibition of FGF signaling reduces neural progenitors. They investigated what would happen in the cerebral cortex where gyrus formation was impaired due to the inhibition of FGF signaling, and found that neural progenitors that produce neurons in the cerebral cortex were much reduced in number (Figure 3).
  4. Inhibition of FGF signaling reduces the number of neurons in the cerebral cortex. Since the reduction was observed in the number of neural progenitors that produce neurons in the cerebral cortex, they next investigated the number of neurons and found that in the superficial layer of the cerebral cortex where FGF signaling was inhibited was particularly reduced in comparison to other layers.

In summary, the study concluded that FGF signaling augments the number of neuronal progenitors and neurons in regions destined to become gyri, and, as a result, gyri, folds of the cerebral cortex, are formed (Figure 3).

Schematic illustration of the cerebral cortex, a sectional view. Among regions of the cerebral cortex, those where a large number of neural progenitors exist would develop gyrus formation (left). By inhibiting FGF signaling, neural progenitors are reduced and gyrus formation is impaired (right), indicating FGF signaling is important for gyrus formation. Credit: Kanazawa University

In the present study, the authors uncovered an important mechanism of gyrus formation in the by using their unique research technique developed for the ferret. In the past, there have been few studies on the mechanisms of gyrus formation with animal models. As mentioned above, the research group succeeded in 2015 in developing a ferret disease model that shows impairment in the gyrus.

It is expected that further studies along these lines should contribute to research on brain evolution, up to that of the human, which has been difficult in the past, and to the investigation of causes and treatment of various diseases of the and the nervous system.

Explore further: Folding of the cerebral cortex—identification of important neurons

More information: Naoyuki Matsumoto et al, Gyrification of the cerebral cortex requires FGF signaling in the mammalian brain, eLife (2017). DOI: 10.7554/eLife.29285

Related Stories

Folding of the cerebral cortex—identification of important neurons

October 5, 2017
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 ...

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 ...

Children with better physical fitness levels have greater volume of gray matter

November 21, 2017
Researchers from the University of Granada (UGR) have proven that physical fitness in children may affect their brain structure, which in turn may have an influence on their academic performance. More specifically, the researchers ...

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 ...

Chicken embryo illuminates role of thyroid hormone in brain development

November 6, 2017
A thyroid hormone transporter is essential for the earliest stages of brain development, according to a JNeurosci study of a region of the developing chicken brain with a layered structure similar to the human cerebral cortex.

Faulty cell signaling derails cerebral cortex development, could it lead to autism?

September 20, 2017
As the embryonic brain develops, an incredibly complex cascade of cellular events occur, starting with progenitors - the originating cells that generate neurons and spur proper cortex development. If this cascade malfunctions ...

Recommended for you

Study suggests mice and rats, like humans, make poor choices based on 'sunk costs'

July 13, 2018
A team of researchers at the University of Minnesota has found that mice and rats, like humans, tend to make poor decisions based on "sunk costs." In their paper published in the journal Science, the group describes their ...

The neurobiology of fruit fly courtship helps illuminates human disorders of motivation

July 13, 2018
Two fruit flies meet in an acrylic mating chamber and check each other out. It's the insect version of speed dating for science.

Fragile X: New drug strategy corrects behavior/biochemical measures in mouse model

July 13, 2018
Research in mice shows that a pharmacological strategy can alleviate multiple behavioral and cellular deficiencies in a mouse model of fragile X syndrome (FXS), the most common inherited form of intellectual disability and ...

Chemicals associated with oxidative stress may be essential to development

July 12, 2018
Some level of molecules linked to oxidative stress may be essential to health and development, according to new animal studies.

The VIPs of the nervous system—a tiny population of neurons holds a master key to the body's clock

July 12, 2018
Travel by airplane has opened the door to experiencing different cultures and exploring natural wonders. That is, if you can get past the jet lag.

Novel therapy delays muscle atrophy in Lou Gehrig's disease model

July 12, 2018
Supplementing a single protein found in the spinal cord could help prevent symptoms of Lou Gehrig's disease, according to a new study out of Case Western Reserve University School of Medicine. Researchers found high levels ...


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.