Revealing the genetic basis responsible for Rett syndrome's development

Kyushu University, one of Japan's leading research-oriented institutes of higher education, has made a significant breakthrough in understanding Rett syndrome, a neurodevelopmental disorder that affects one in every 10,000 to 15,000 female births.

Located in Fukuoka City, a coastal metropolis on the southwestern Japanese island of Kyushu, Kyushu University is home to around 19,000 students and 8,000 faculty and staff. The university's world-class research centers cover a wide range of study areas and research fields, from the humanities and arts to engineering and medical sciences.

The research, published in the prestigious journal Cell Reports in 2021, was led by a team of researchers including Hideyuki Nakashima, Keita Tsujimura, and others. The team's findings provide insight into the roles of MeCP2, miR-199a, and BMP signaling in the pathology of Rett syndrome.

Rett syndrome is characterized by impairments in cognition and coordination. The gene responsible for Rett syndrome is called methyl-CpG binding protein 2, or MeCP2. Deficiencies in key genes involved in the pathology of Rett syndrome cause neural stem cells to generate less neurons by producing more astrocytes, the support cells of the brain that help maintain everything else while neurons fire off electrical signals.

The team found that a microRNA called miR-199a, when disrupted, increases the production of astrocytes. 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.

The team was able to reduce abnormal neural stem cell differentiation by inhibiting BMP in a brain organoid culture. This suggests that targeting BMP signaling could potentially lead to clinical treatments for Rett syndrome symptoms.

Further investigation is needed to confirm these findings and potentially pave the way for new treatments for Rett syndrome. The research linking the genetic cause to the neurophysiological disorder in Rett syndrome was published by Prof. Dr. Huda Zoghbi and her team, who are recognized for their work on the causes of Rett syndrome in the Jan and Dan Duncan Neurological Research Institute.

Kyushu University continues to be at the forefront of groundbreaking research, contributing significantly to our understanding of various diseases and disorders, and working towards the development of new treatments and therapies.