Discovering Cell Type Specific Functions of The Extracellular Matrix in the Central Nervous System in Development and Disease

The cerebral cortex relies on the precise development of its enormous diversity of neuronal cell types. To this end, cells integrate intrinsic genetic programs with extrinsic signals. While the genetic programs are well understood, the extrinsic mechanisms, including interaction with the extracellular matrix (ECM) and neighbouring cells, are underexplored. However, the complex and diversified ECM suggests that it can act as an additional layer controlling cell identity. My lab will elucidate how the ECM contributes to neuronal diversification during typical development and in neurodevelopmental disorders. During this fellowship, we will establish the foundations of a cell-type specific ECM code and its impact on neuronal identity by characterizing 1) the expression and production of neuronal-type specific ECM, 2) their function in the acquisition of neuronal features, including molecular profile, migration and axon extension, 3) the underlying gene regulatory mechanisms, and 4) the differences in ECM composition in the context of autism spectrum disorders in a Spanish speaking, Latin American patient sample. Understanding the ECM function will unlock an additional layer of regulation, and contribute to the aetiology of neurodevelopmental disorders. Additionally, I will build capacities, and train human resources to make single cell technologies more broadly available in Latin America.