Molecular analysis of the non-cell autonomous effects in Down syndrome cortex using mouse ESC-derived brain organoids

Down syndrome (DS) is the most frequent genetic cause of intellectual disability due to trisomy of human chromosome 21. In the brain, the pathological sequelae of trisomy 21 results in intellectual disability in infants as well as early onset dementia in adults.  The brain is a highly integrated organ, in which each neuron is connected in a very specific manner into a neuronal circuitry, and where its niche (i.e. glia-neuron interaction and excitation-inhibition) is central to regulate the proper function of intellectual and cognitive capacities. However, very few studies have explored the role of microenvironment on brain development.  For this, the project focuses on dissecting the specific non-cell autonomous molecular mechanisms that contribute to the pathogenesis of DS.