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Role of the vasculature in neuronal migration. 'The neurovascular link'

Final Report Summary - NEUROVASCULAR LINK (Role of the vasculature in neuronal migration. 'The neurovascular link')

During CNS development and adult neurogenesis, immature neurons travel from the germinal zones towards their final destination using cellular substrates for their migration. Classically, radial glia and neuronal axons have been shown to act as physical scaffolds to support neuroblast locomotion in processes known as gliophilic and neurophilic migration, respectively. Recent studies highlight a novel mode of neuronal migration that uses blood vessels as scaffolds, the so-called vasophilic migration. This migration mode allows neuroblasts navigation in physiological and also pathological conditions, such as neuronal precursors migration after ischemic stroke or cerebral invasion of glioma tumor cells. In our project we have investigated the molecular crosstalk between neurons and vessels during embryonic development and the formation of the neurovascular unit. Our results have identified a signaling pathway important for this communication. Vascular specific mutations of this pathway have shown defects in cortical development as well as altered blood brain barrier integrity.
Many neurological and psychiatric diseases have a vascular component but there is little scientific progress concerning the molecular players that regulate both the vascular and the nervous system. Therefore, from our findings emerge a novel molecule involved in angiogenesis which might have a potential therapeutic application in vascular related diseases of the CNS. Furthermore, its participation in blood brain barrier integrity opens the possibility to be used as pharmacological tool to regulate the blood brain barrier permeability. Overall, our data has a high impact in the current knowledge of CNS development and our findings might be transferred to the development of new pharmacological drugs for neurological and psychiatric pathologies.