Examining the genetic basis responsible for Rett syndrome

In a groundbreaking discovery, a team of researchers at Kyushu University, one of Japan's leading research-oriented institutes of higher education, have identified a possible genetic pathway behind the neurological dysfunction of Rett syndrome. The research, published in the prestigious journal Cell Reports, was conducted by a group of scientists led by Kinichi Nakashima.

The team, which includes Hideyuki Nakashima, Keita Tsujimura, Koichiro Irie, Takuya Imamura, Cleber A. Trujillo, Masataka Ishizu, Masahiro Uesaka, Miao Pan, Hirofumi Noguchi, Kanako Okada, Kei Aoyagi, Tomoko Andoh-Noda, Hideyuki Okano, Alysson R. Muotri, and Kinichi Nakashima, established a brain organoid culture from iPS cells derived from patients with Rett syndrome. They were able to reduce abnormal neural stem cell differentiation by inhibiting BMP, providing valuable insights into the role of MeCP2, miR-199a, and BMP signaling in the pathology of Rett syndrome.

Rett syndrome is a neurodevelopmental disorder that occurs in roughly one in every 10,000 to 15,000 female births. It is caused by mutations in a gene called methyl-CpG binding protein 2, or MeCP2. When either MeCP2 or miR-199a are disrupted, it increases the production of cells called astrocytes. Astrocytes are support cells of the brain that help maintain everything else while neurons fire off electrical signals. However, an imbalance in the production of these cells can lead to the neurological symptoms associated with Rett syndrome.

The researchers found that a microRNA called miR-199a, associated with MeCP2, affects the differentiation of neural stem cells. Smad1, a transcription factor critical for proper cellular development, functions downstream of a pathway called BMP signaling, which is known to inhibit the production of neurons and facilitate the generation of astrocytes. By inhibiting BMP, the team was able to reduce the abnormal differentiation of neural stem cells observed in Rett syndrome.

Kinichi Nakashima, the team leader, concludes that the research provides valuable insights into the role of MeCP2, miR-199a, and BMP signaling in the pathology of Rett syndrome. The team hopes that further investigation can lead to clinical treatments for Rett syndrome symptoms.

Fukuoka City, where Kyushu University is located, is frequently ranked among the world's most livable cities. The university's world-class research centres cover a wide range of study areas and research fields, from the humanities and arts to engineering and medical sciences. The authors who conducted the experiment identifying the genetic disorder behind the neurological disorder of Rett syndrome belong to a research group including Huda Zoghbi at Baylor College of Medicine.

The title of the research paper is "MeCP2 controls neural stem cell fate specification through miR-199a-mediated inhibition of BMP-Smad signaling." The research paper's DOI is 10.1016/j.celrep.2021.109124.

Kyushu University is home to around 19,000 students and 8,000 faculty and staff, and its multiple campuses are located around Fukuoka City, a coastal metropolis on the southwestern Japanese island of Kyushu. The university's commitment to research and innovation continues to drive advances in understanding complex disorders like Rett syndrome, offering hope for those affected by this neurological condition.