Skip to main content

Neurovascular Interactions and Pathfinding in the Spinal Motor System

Periodic Report Summary 2 - NEVAI (Neurovascular Interactions and Pathfinding in the Spinal Motor System)

Nerves and blood vessels establish congruent networks using a shared set of guidance molecules. Neurovascular interactions are critical for nervous system physiology and become deregulated in a variety of neurological and degenerative disorders. Nevertheless, the developmental mechanisms underlying crosstalk between neurons and vasculature are poorly understood. This proposal focuses on motor neurons that reside in the spinal cord – essential for neuromuscular connectivity – and their interactions with vascular endothelial cells that line blood vessels. The endothelium is not simply a conduit for blood supply but has emerging roles in organogenesis and regeneration mediated by mutual signaling interactions with neighboring cells.
We have been using chemical mutagenesis in GFP-reporter mice to identify genes that regulate neurovascular communication in the motor systems and control precise targeting of motor nerves to muscle targets. Cell-based assays and proteomics are unmasking the mechanisms of action of regulators of motor-vessel interactions and axon pathfinding. High-throughput gene profiling of motor neurons and endothelial cells is revealing their molecular signatures and inform selection of candidate mediators of neurovascular communication, which are further screened through co-culture systems and biochemical methods. Our studies are (i) supporting an instructive role for neurovascular signaling in the assembly of neuronal connections during embryo development, (ii) unmasking neurovascular pathways that mediate region-specific crosstalk with nerve cells, (iii) identifying novel regulatory mechanisms for high-fidelity axon pathfinding based on molecular switches that impose spatiotemporal control to guidance responses.