NEUROVASCULAR LINK · Role of the vasculature in neuronal migration. 'The neurovascular link'
FP7 — People (Marie Curie Actions)
- Duration
- 2011-09-01 → 2016-01-31
- EU contribution
- €100,000
- Participants
- 1
- Scheme
- MC-CIG
Lines connect the coordinator with its partners.
Results in brief
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.
Data: CORDIS, © European Union
Project objective
A fascinating characteristic of the anatomy of the vascular system is that blood vessels exhibit a high similarity in their branching pattern and often a remarkable alignment to nerve fibers. This parallel wiring of the vascular and the nervous system might reflect its mutual dependence and also might indicate mutual guidance phenomena, with vessels providing the signals and the scaffold for growing nerves and nerves secreting angiogenic cues to guide developing vessels.The main goal of this project is to elucidate the molecular mechanisms by which blood vessels may lead the neurons to achieve proper positioning at the developing brain and the molecular cues that are involved in this guidance process. More precisely, we will explore the role of the vasculature on neuronal migration via the Reelin pathway. Reelin is a large, secreted glycoprotein that acts as a guidance molecule on migrating neurons to regulate their proper positioning during brain development. Reelin binds to two lipoprotein receptors, VLDLR and ApoER2, and induces the phosphorylation of the adaptor protein Dab1. Mice that lack Reelin expression (Reeler mice) exhibit severe neuropathological abnormalities. Our preliminary data identifies Reelin as an angiogenic factor and is the basis for an exciting project that aims at studying Reelin as a putative angioneurin, a novel concept of molecules that affects both neural and vascular cell processes. To explore this we will design an endothelial specific Dab1 null mice (Tie2Dab1-/-) to study the loss of function of Reelin selectively on endothelial cells and we will study the contribution of the vasculature to the nervous system defects in the reeler phenotype. This project will contribute to elucidate the molecular basis of the neurovascular link in health and disease and further contribute to the emerging research on the neurovascular development.
Original text from CORDIS.
Participants
- JOHANN WOLFGANG GOETHE-UNIVERSITAET FRANKFURT AM MAIN · Frankfurt Am MainCoordinatorGermany
Links
Data: CORDIS, © European Union