Defining signalling pathways that control neurovascular interactions in the brain and retina. (360G-Wellcome-095623_Z_11_Z)

Cell cell adhesion and signalling between neural and vascular cells in the central nervous system (CNS) control brain and retinal development, regulate traffic across the blood-brain and blood-retinal barriers and neurogenesis in adults. Consequently, dysfunctional neurovascular interactions cause congenital vascular malformations or contribute to neurodegenerative diseases, such as ischemic stroke and the chronic eye diseases diabetic retinopathy and age-related macular degeneration. To date, a poor understanding of the molecular and cellular mechanisms that control neurovascular interactions has hampered our ability to treat such conditions. My team will build upon complementary expertise in vascular and neuronal pattern formation to explore three outstanding questions on neurovascular interactions in the brain and retina. We will address how neural cells guide new blood vessel growth to optimise their own function; how blood vessels and vascular growth factors modulate the product ion of new neurons by neurogenesis; and how pathways that activate both angiogenesis and vascular permeability may be functionally dissociated to regulate neurovascular barriers in the brain and retina. The specific aims of this proposal are to: 1. Identify the molecular mechanisms that integrate blood vessels into the developing brain and retina. 2. Identify the molecular mechanisms that place neural progenitors into a vascular stem cell niche. 3. Define novel pathways that regulate vascular permeability in the brain and retina. Accomplishing these aims will provide fundamental knowledge about normal brain and retinal development and chronic neurovascular disease. In addition, by placing the traditionally separate fields of angiogenesis, neurogenesis and vascular barrier regulation into a larger framework of regulatory interactions, we will bring forward the development of effective therapies for CNS repair and regeneration in neurovascular disease.