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Neurovascular Interactions and Pathfinding in the Spinal Motor System

Objective

"Neurons and blood vessels rely on common guidance signals to wire into elaborate neural and vascular networks that are closely juxtaposed and interdependent: vascular supply of oxygen and nutrients is essential to sustain the high metabolic rate of the nervous system, and conversely neural control of vascular tone is crucial for circulatory homeostasis. However, it remains unclear how the nervous and vascular systems establish an intimate physical and functional relationship. This proposal seeks to reveal the developmental mechanisms that link neuronal connectivity and vascularization of the nervous system, focusing on the interactions between vascular endothelial cells and spinal motor neurons that control locomotion, respiration and autonomic responses. Motor neuron diseases and a variety of other neurodegenerative conditions are precipitated by vascular abnormalities. Thus, understanding the molecular basis of neurovascular crosstalk may offer novel therapeutic opportunities.
My group will use mutagenesis-based forward genetics in reporter mice combined with gene profiling of motor neurons and endothelial cells to screen for novel regulators of neurovascular interactions and pathfinding. Candidate genes will be further characterized using in vivo mouse and chick models, in addition to in vitro studies to uncover the mechanisms of action. Through this multi-disciplinary approach, the proposal will address these fundamental questions: (i) Do neurovascular interactions instruct the assembly of neural and vascular networks? (ii) What signaling pathways connect region-specific vascularization of the CNS to the local metabolic and functional demand of neuronal tissues? (iii) What mechanisms account for specificity, spatiotemporal control and integration of guidance signaling? In addition, this research plan will generate comprehensive transcriptional/proteomic datasets and novel mouse mutants for future studies of neurovascular communication and patterning."

Field of science

  • /medical and health sciences/basic medicine/physiology/homeostasis
  • /natural sciences/biological sciences/genetics and heredity

Call for proposal

ERC-2013-StG
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

OSPEDALE SAN RAFFAELE SRL
Address
Via Olgettina 60
20132 Milano
Italy
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
EU contribution
€ 1 653 000
Principal investigator
Dario Bonanomi (Dr.)
Administrative Contact
Maria Rosa Pedrazzi (Dr.)

Beneficiaries (1)

OSPEDALE SAN RAFFAELE SRL
Italy
EU contribution
€ 1 653 000
Address
Via Olgettina 60
20132 Milano
Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
Principal investigator
Dario Bonanomi (Dr.)
Administrative Contact
Maria Rosa Pedrazzi (Dr.)