Neuron-glia interactions are key for proper myelination in the brain and for its functionality. To study neuron-glia interaction roles in brain development we focus on the genetic disorder Williams syndrome (WS). WS is a multisystemic neurodevelopmental disorder caused by a de-novo hemizygous deletion of ~26 genes from chromosome 7q11.23. We previously revealed surprising aberrations in myelination and brain development in a novel mouse model for the hypersociability phenotype associated with WS, as a result of a neuronal deletion of the transcription factor Gtf2i, which is one of the genes deleted in WS. In this talk, I will present our recent findings focused on altered white matter and brain development in WS, and discuss potential molecular and cellular explanations for the neurodevelopmental deficits in WS. Specifically, I will present evidence for mitochondrial dysfunction in neurons, and what are the microglial responses to the resultant myelination deficits. Furthermore, to study the implication of our studies from mouse models on human condition, I will show our new data on the altered epigenome of human frontal cortex tissue from WS compared to controls. Finally, I will present our approaches to develop new therapeutic approaches and will update on our clinical trial focused on ameliorating white matter deficits in WS. Hybrid seminar Zoom link: https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09 Meeting ID: 954 0689 3197 Password: 750421