March 17, 2017 Left: Cross-sectional view of the cerebrum in normal ferret. Neurons are localized in the cerebral cortex, the surface layer of the cerebrum. Since the surface of the cerebrum has folds (gyri), the layer containing neurons winds on its way. Right: Cross-sectional view of the cerebrum in TD ferret. Clusters of neurons (indicated by arrows) are found deep in the cerebrum, which are not detected in the cerebrum of normal ferret. They are called 'periventricular nodular heterotopia,' PNH. In addition, in the surface layer, a larger number of smaller folds (gyri) are seen than normal (indicated by asterisks). They are called polymicrogryri. Credit: Kanazawa University

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 discovered that neuronal translocation along radial glial fibers to the cerebral cortex during fetal brain development is aberrant, suggesting the cause underlying TD.

In TD cases, the limb and rib bones are shorter than normal, and brain abnormalities manifest, including polymicrogyria and periventricular nodular heterotopia. Previous research has determined that a gene, fibroblast growth factor receptor 3 (FGFR3), is responsible. However, as a result of TD rarity and the difficulty of obtaining brain samples from human patients, the pathophysiology of TD is largely unknown, and effective therapy has not been established.

The present research team of Kanazawa University generated an animal model of TD using ferrets that reproduces the brain abnormalities found in human TD patients. By using this animal model, the team elucidated the formation process of polymicrogyria, one of the abnormalities found in the TD brain. The team has also investigated the formation process of PNH, the other brain abnormality found in human TD patients.

First, PNH was analyzed in terms of composing cell types to reveal that a large number of neurons but few glial cell exist in PNH. In a healthy brain, neurons are found in the cerebral cortex near the brain surface. The researchers believe that during fetal brain development, PNH formation might be induced by the inability of neurons to translocate themselves to the cerebral cortex. The researchers found that the spatial arrangement of radial glial cells was distorted; radial glial fibers are believed to serve as the "track" for neurons to translocate themselves. Thus, the distortion of radial glial fibers seems to be a reason for aberrant localization of neurons.

Research on abnormalities of bones in TD is progressing with iPS cells at Kyoto University, and it is expected that the whole aspect of TD with brain and bone abnormalities would be elucidated and that the therapeutic methods would be developed. The present study on PNH was only possible using the experimental technique for ferrets developed by the research team. This animal model technique could also contribute to studies of other neurological diseases that have been difficult to investigate with conventional model animals.

Explore further: Researchers discover a gene's key role in building the developing brain's scaffolding

More information: Naoyuki Matsumoto et al, Pathophysiological analyses of periventricular nodular heterotopia using gyrencephalic mammals, Human Molecular Genetics (2017). DOI: 10.1093/hmg/ddx038

(Medical Xpress)Researchers have pinpointed the role of a gene known as Arl13b in guiding the formation and proper placement of neurons in the early stages of brain development. Mutations in the gene could help explain ...

A protein that may partly explain why human brains are larger than those of other animals has been identified by scientists from two stem-cell labs at UC San Francisco, in research published in the November 13, 2014 issue ...

Today, a stroke usually leads to permanent disability but in the future, the stroke-injured brain could be reparable by replacing dead cells with new, healthy neurons, using transplantation. Researchers at Lund University ...

Research on fragile X syndrome, the most common inherited cause of mental retardation, has focused mostly on how the genetic defect alters the functioning of neurons in the brain. A new study focusing on a different type ...

Zika's hypothesized attraction to human neural stem cells may come from its ability to hijack a protein found on the surface of these cells, using it as an entryway to infection. In Cell Stem Cell on March 30, researchers ...

The difference between an old brain and a young brain isn't so much the number of neurons but the presence and function of supporting cells called glia. In Cell Reports on January 10, researchers who examined postmortem brain ...

The majority of genes associated with nephrotic syndrome (NS) in humans also play pivotal roles in Drosophila renal function, a conservation of function across species that validates transgenic flies as ideal pre-clinical ...

Britain's Newcastle University says its scientists have received a license to create babies using DNA from three people to prevent women from passing on potentially fatal genetic diseases to their childrenthe first time ...

Columbia University Medical Center (CUMC) researchers have discovered a common genetic variant that greatly impacts normal brain aging, starting at around age 65, and may modify the risk for neurodegenerative diseases. The ...

Studies of autoimmune and inflammatory diseases have identified hundreds of genetic regions thought to be associated with these conditions. At the same time, studies of expression quantitative trait loci (eQTLs) have revealed ...

Scientists studying the role of a protein complex in the normal development of the mouse brain unexpectedly created a mouse model that replicates clinical symptoms of patients with complex neurological disorders such as hyperactivity, ...

Genetic variation in the non-coding DNA could give rise to language impairments in children and other neurodevelopmental disorders including schizophrenia, autism, and bipolar disorder, scientists from the Max Planck Institute ...

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

More here:
Researchers develop new animal model to study rare brain disease - Medical Xpress

Comments are closed.