Defects in neuronal migration have a severe impact on normal brain function. Here, neuronal contact sensing of the extracellular environment combines with complex signaling, determining the final wiring and plasticity. Although deficits in neuronal micro-connectivity are recently emerging as crucial in neurodevelopmental disorders (e.g. autism, schizophrenia), the role of neuronal sensing and fine-migration processes is still poorly understood in these pathological conditions.
The project will focus on the unbalanced levels of ubiquitin ligase E3a (UBE3A), which leads to several neurodevelopmental disorders, such as Angelman Syndrome and autism. However, its specific role in brain development is still unclear.
The obtained results will help to clarify the role of UBE3A in the pathogenesis of neurodevelopmental disorders but also to establish the value of nano-engineered platforms as innovative bio-mimicking platforms for investigating neuronal guidance dynamics in vitro, at molecular level.