Rett syndrome is a progressive neurodevelopmental disorder characterized by 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.

In their past research, the team had identified that MeCP2 acts as a regulator for the processing of specific microRNAs to control the functions of neurons. So, they went back to investigate if that pathway was also involved in the differentiation of neural stem cells.

Astrocytes are like the support cells of your brain. While neurons fire off the electrical signals, astrocytes are there to help maintain everything else. 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. 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. To investigate the process further, the team established a brain organoid culture a 3D culture of neural stem cells that can mimic aspects of brain development from iPS cells derived from patients with Rett syndrome. When they inhibited BMP, short for bone morphogenetic protein, the team was able to reduce abnormal neural stem cell differentiation.

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John
EditorialAssistant
Immunogenetics Open Access