The molecular signature of Rett syndrome

Rett Syndrome (RTT) is a neurodevelopmental disorder resulting from mutations in the MECP2 gene. Although symptoms manifest after birth, the disorder is thought to affect brain development prenatally. This thesis studied RTT using brain organoids, which are miniature brain models that replicate normal and diseased brain development. By analysing these organoids, this thesis demonstrated that there are dynamic changes in gene and protein levels in RTT brain organoids, pointing to early disruptions in neuronal pathways well before the clinical onset of the disease. Furthermore, we also revealed that brain cell communication via extracellular vesicles is altered. Extracellular vesicles are small particles that cells use to transfer message to each other. The changes in the content of these vesicles, as discovered in this thesis, could serve as potential prognostic biomarkers for the disease. In summary, this work provides a comprehensive understanding of the molecular underpinnings of RTT and opens avenues for future research and potential therapies.