Alvin Huang, MD PhD Submitted: This presentation will discuss how brain cells communicate during development and how this communication may be disrupted when the gene UBE3A is lost in neurons. Using human stem cell-based neuron and microglia models, Angelman syndrome mouse tissue, and analysis of an Angelman syndrome pig brain dataset, I will show how neuronal UBE3A loss may trigger inflammatory signals that change how microglia, the brain’s immune cells, respond to developing synapses. The talk will also discuss how targeting TNF/TNFR signaling may help calm these abnormal neuroimmune responses, with possible relevance to Angelman syndrome and other neurodevelopmental disorders.