Scientists unravel the genetic mechanism behind the Rett Syndrome

Scientists unravel the genetic mechanism behind the Rett Syndrome
Research conducted by Kyushu University has found a possible genetic pathway behind the neurological dysfunction of Rett syndrome. The team discovered that deficiencies in key genes involved in the pathology, triggers neural stem cells to generate fewer neurons by producing more astrocytes — the brain’s maintenance cells. The study was published in the journal, Cell Reports.
Rett syndrome is a neurodevelopmental disorder which causes impairments in cognition and coordination — with varying severity — and occurs in roughly one in every 10,000 to 15,000 female births. However, it is difficult to initially identify because children appear to develop normally in the first 6-18 months.
“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,” explains first author Hideyuki Nakashima of Kyushu University’s Faculty of Medical Sciences.
“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,” says Nakashima. “In fact, when either MeCP2 or miR-199a are disrupted, we found that it increased the production of cells called astrocytes.”
MicroRNAs or miRNAs regulate messenger RNA to make sure the cell is making the correct amount of the desired protein. Astrocytes are like the support cells of the brain. During development, astrocytes and neurons are generated from the same type of stem cells, known as neural stem cells, where their production is carefully controlled. However, dysfunction in MeCP2 or miR-199a causes these stem cells to produce more astrocytes than neurons.

Nakashima said that further analysis revealed that miR-199a targets the protein Smad1 which is responsible for proper cellular development. Smad1 also functions downstream of a pathway called BMP signaling, which is known to inhibit the production of neurons and facilitate the generation of astrocytes.

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