NEUROGUIDE · Study of neuronal sensing and migration/guidance dynamics in neurodevelopmental disorders by nano-engineered chips

Study of neuronal sensing and migration/guidance dynamics in neurodevelopmental disorders by nano-engineered chips

Defects in neuronal migration have a severe impact on normal brain function. Although deficits in neuronal micro-connectivity are recently emerging as crucial in neurodevelopmental disorders and intellectual disabilities (e.g. autism), the role of neuronal migration processes during brain development is still poorly understood in these pathological conditions. NEUROGUIDE project aims to study neuronal migration/guidance dynamics in neurodevelopmental disorders, with a multidisciplinary approach that combines nano-engineered devices (i.e. nano-structured substrates and microfluidic chips), molecular neuroscience and state-of-the-art fluorescence microscopy. As a pathological model, the project focus on the unbalanced levels of ubiquitin ligase E3a (UBE3A), which leads to several neurodevelopmental disorders. UBE3A has a key role in the brain. In fact, the lack of UBE3A leads to Angelman Syndrome (AS), while its increase is the most prevalent genetic origin of autism (≈ 3%). However, the specific role of UBE3A in brain development is still not known and there is no cure for AS or autistic disorders currently available. These disorders do not only affect the patients but are also a great burden on families and on the healthcare system. NEUROGUIDE project aims to study the neuronal responses to guidance stimuli bi-directionally: 1) in vivo, in Ube3a-mutant mice (using in utero electroporation), to identify if the UBE3A loss/increase impacts neuronal migration and guidance during brain development; 2) in vitro, in Ube3a-mutant neurons by using nano-engineered platforms to apply specific biomimetic environmental physical and/or chemical stimuli to neurons: this approach allows studying the biochemical mechanisms involved in the neuronal guidance processes, at the molecular level (Fig.1). The objectives of NEUROGUIDE project are: - to clarify the role of UBE3A (and its isoforms) in neurodevelopment; - to establish the value of nano-engineered platforms as advanced devices for investigating neuronal guidance dynamics in vitro. These bio-mimicking platforms can be exploited as read-out systems for in vitro testing of novel potential drugs, thus helping in the application of the 3Rs principles.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз