Categories
Health|Others

Could This Be The End To Developmental Disorders?

Using a new type of genetic engineering tool called epigenome editing in mice, scientists have restored irregularities in the developing brain that arise from a gene mutation.

Epigenome editing is a way of altering the expression, or reading, of genes without altering their underlying DNA code.

A team from Johns Hopkins University in Baltimore, MD, led the Nature Communications study that focuses on the protein C11orf46.

One of the study’s corresponding authors is Dr. Atsushi Kamiya, who is an associate professor of psychiatry and behavioral sciences at Johns Hopkins University School of Medicine.

In humans, mutations in the section of DNA that contains the C11orf46 gene can lead to WAGR syndrome, a genetic condition that can cause intellectual disability and impair many systems of the body.

The researchers found that C11orf46 directs the development of the corpus callosum, which is the complex bundle of nerve fibers that connects the right and left sides of the brain.

If the corpus callosum does not form correctly, it can give rise to brain development disorders, such as autism, and the type of intellectual disability that can occur in WAGR syndrome.

Gene silencing

Another name for WAGR syndrome is chromosome 11p13 deletion syndrome because the mutations that cause it comprise deletions of DNA in a specific region of chromosome 11. The C11orf46 gene sits in this region.

To study the effect of missing C11orf46 protein, the researchers silenced its coding gene in mice.

Instead of deleting the gene directly, however, they reduced its expression using an epigenome editing tool.

With this tool, scientists can alter the chromatin packaging of DNA rather than the DNA code itself.

This alteration makes it harder for a cell’s DNA readers to read the protein’s DNA code, with the result that the cell produces less of it.

The team found that mice that made less C11orf46 protein failed to develop the corpus callosum correctly in their brains. The brain impairment is similar to that which occurs in WAGR syndrome.

Epigenome editing restored axon bundling

When the researchers took a closer look, they found that mice that produced less C11orf46 protein had higher expression in the gene that makes another protein called Semaphorin 6A.

Semaphorin 6A has a key role in guiding the direction of growth of neuronal axons in the developing brain.

With further epigenome editing that altered the expression of its associated gene, SEMA6A, the researchers were able to reduce Semaphorin 6A in the mice and restore the bundling of neuron axons to resemble that of normal mice.

“RNA-guided epigenetic editing of Sema6a gene promoters via a dCas9-SunTag system with C11orf46 binding normalized SEMA6A expression and rescued transcallosal dysconnectivity via repressive chromatin remodeling by the SETDB1 repressor complex,” write the authors.

The researchers conclude that the study demonstrates how precise epigenetic editing of chromatin can alter the early development of the connection between the right and left brain.

“Although this work is early, these findings suggest that we may be able to develop future epigenome editing therapies that could help reshape the neural connections in the brain, and perhaps prevent developmental disorders of the brain from occurring.”

Dr. Atsushi Kamiya

Src: Medical News Today

Leave a Reply

Your email address will not be published. Required fields are marked *