Determining the cellular basis of a neurodevelopmental disease: MeCP2 dysfunction in glia and neurons

Neurodevelopmental disorders such as Rett syndrome (RTT) arise from disruptions in brain development, often linked to mutations in MeCP2, a transcriptional regulator. While neuronal dysfunction is considered central to RTT, MeCP2 is also abundant in glia, suggesting broader contributions. Using co-culture systems and transgenic mice, this work demonstrates that non-cell autonomous signaling between neurons and astrocytes significantly influences RTT phenotypes. Additionally, we identify a regulatory pathway controlling MeCP2 levels and a developmental window sensitive to its function. These findings highlight the importance of neuron-glia interactions in RTT and inform future therapeutic strategies.