JUL 04, 2021 5:48 AM PDT

New Insights Into the Mechanisms of Rett Syndrome

WRITTEN BY: Carmen Leitch

Rett syndrome is a neurological disorder that mostly affects girls; affected individuals develop normally until they're between six and eighteen months old. Development then begins to slow, and the disorder can be difficult for clinicians to identify because the initial symptoms are vague, like a reduced interest in toys and a lack of eye contact. Eventually the issues become more severe, and problems with movement may arise. The disease varies in presentation and severity, but many cases trace back to mutations in a gene called methyl CpG binding protein 2 (MECP2).

Image credit: Max Pixel

Scientists have now learned more about the biological basis of the disorder, which occurs in about one female birth in about 12,500. The research has been published in Cell Reports.

"Rett syndrome is caused by mutations in a single gene called methyl-CpG binding protein 2, or MeCP2. The gene was identified over two decades ago and much has been uncovered since, but exactly how the mutations cause the pathology remains elusive," explained first study author Hideyuki Nakashima of Kyushu University.

Previous work by Nakashima's team has suggested that MeCP2 is involved in regulating molecules called microRNAs that are associated with neurons. MicroRNAs do not code for protein like messenger RNA molecules do; microRNAs can play regulatory functions in a cell, like whether a gene expresses a protein.

In this work, the researchers determined that when there are disruptions in MeCP2, the brain does not produce as many cells called astrocytes as they normally would. Astrocytes are known as support cells for neurons but research has indicated they also have other functions.

Brain organoids generated from control (top) and Rett syndrome (left) patients, including astrocytes (cyan). Color intensity is higher in Rett-derived organoids./ Credit: Kyushu University/Nakashima Lab

Neural stem cells can give rise to astrocytes or neurons, and the production of these cell types, or the differentiation of neurons, is carefully controlled. But when there are problems with either MeCP2 or a microRNA called miR-199a, a culture of neural stem cells will produce more astrocytes and fewer neurons.

"Through our investigation, we found several microRNAs associated with MeCP2, but only one affected the differentiation of neural stem cells: a microRNA called miR-199a," said Nakashima. "In fact, when either MeCP2 or miR-199a are disrupted, we found that it increased the production of cells called astrocytes."

The scientists also learned more about the mechanisms that were at work. "Further analysis showed that miR-199a targets the protein Smad1, a transcription factor critical for proper cellular development. Smad1 functions downstream of a pathway called BMP signaling, which is known to inhibit the production of neurons and facilitate the generation of astrocytes," added Nakashima.

When the researchers inhibited BMP in a three-dimensional cell culture model, abnormal neuronal differentiation was reduced.

"Our findings have given us valuable insight into the role of MeCP2, miR-199a, and BMP signaling in the pathology of Rett syndrome," said Nakashima. "Further investigation is needed, but we hope this can lead to clinical treatments for Rett syndrome symptoms."

Sources: AAAS/Eurekalert! via Kyushu University, Cell Reports

About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
NOV 09, 2021
Health & Medicine
How to Search the Cyagen Knockout Catalog Models Resource?
NOV 09, 2021
How to Search the Cyagen Knockout Catalog Models Resource?
The Cyagen Knockout Catalog Models repository provides researchers in the Americas and Europe with ready-to-use knockout ...
NOV 07, 2021
Microbiology
Studying the Genetic Impact of a Common Viral infection
NOV 07, 2021
Studying the Genetic Impact of a Common Viral infection
Human cytomegalovirus (HCMV) infects many people; it's been estimated that by the time people are adults, about half of ...
NOV 12, 2021
Genetics & Genomics
First Results From 100,000 Genomes Project Gives Hundreds Their Answer
NOV 12, 2021
First Results From 100,000 Genomes Project Gives Hundreds Their Answer
The UK's 100,000 Genomes Project has now given hundreds of people a diagnosis for their disease. Many of them have been ...
DEC 15, 2021
Microbiology
A Genetic Modification Alters Bacterial Behavior to Produce Artistic Swirls
DEC 15, 2021
A Genetic Modification Alters Bacterial Behavior to Produce Artistic Swirls
Researchers engineered a genetic circuit to make pathogenic bacteria called Myxococcus xanthus move in swirled patterns.
JAN 25, 2022
Genetics & Genomics
History of Creating Genetically Humanized Mice
JAN 25, 2022
History of Creating Genetically Humanized Mice
Animal research models are only as effective as their ability to simulate human disease.  Depending on the conditio ...
JAN 25, 2022
Genetics & Genomics
Genetic Causes of Cerebral Palsy are Discovered
JAN 25, 2022
Genetic Causes of Cerebral Palsy are Discovered
Cerebral palsy (CP) starts in early childhood, and is a motor impairment that does not progress. CP is caused when child ...
Loading Comments...