The UBE3A gene codes for an E3 ubiquitin ligase and is critical to ensure a proper brain function. Indeed, perturbations of UBE3A dosage or function result in pathological phenotypes. Loss of UBE3A causes the Angelman Syndrome, a severe neurodevelopmental disorder characterized by intellectual disability, motor delay and seizures, while increased UBE3A copy number or activity are strongly associated with Autism. Importantly, the molecular underpinnings of UBE3A-associated pathogenic mechanisms of neurodevelopmental disorders are still poorly understood. In this project, we study the effects of changes in UBE3A dosage, mimicking the genetic alterations of the Angelman syndrome (or autism) on the regulation of synaptic development at single cell level in vivo. To this aim, we combine cortex-directed in utero electroporation to inactivate UBE3A in sparse layer 2/3 pyramidal neurons with high-resolution optical microscopy to investigate the consequences of UBE3A loss on the functional organization of excitatory and inhibitory postsynaptic compartments. As already suggested by other groups, our results indicate that UBE3A critically regulates the formation of excitatory synapses. Strikingly, our data also suggests that UBE3A controls the assembly and the maturation of specific subtypes of inhibitory synapses, namely those located in the perisomatic region and in the axon initial segment. Together, our preliminary results suggest for the first time that the UBE3A gene may be critical to set the number of excitatory and inhibitory synaptic connections at the single-cell level, thus contributing to regulate the ratio between excitation and inhibition through cell-autonomous mechanisms.