The interaction between vasculature and the central nervous system during embryonic development is essential for the formation of the Blood Brain Barrier (BBB). As endothelial cells sprout in the neuronal tissue they lose fenestrations and acquire key features such as tight junctions. The BBB maintains critical brain homeostasis, limiting the entry of toxins, drugs and pathogens into the brain. In this proposal we want to analyze the signaling pathway miR-107 dependent linking neurogenesis to the vascular and BBB maturation. We propose to investigate 1) how neural stem cells and their number influence the BBB stabilization;2) why neural miR-107 positive cells are required for vascular permeability;3) finally the miR-107 downstream signaling pathways that affect neurovascular homeostasis. We propose that miR-107 is a novel neural miRNA required for normal neurogenesis and vascular stabilization. Interestingly, miR- 107 has be appointed as a potential therapeutically target for Diabetes and other neurodegenerative diseases. Therefore, we believe that the studies proposed in this grant are necessary to evaluate the pros and cons of future miR-107-therapies.

Public Health Relevance

This grant proposal aims to investigate the interaction between neural stem cells and vascular network during the development of the blood brain barrier. In particular, we will focus on the miR-107 dependent signaling pathways that link neurogenesis and vascular permeability.

Agency
National Institute of Health (NIH)
Type
High Priority, Short Term Project Award (R56)
Project #
1R56HL123998-01
Application #
8903529
Study Section
Cardiovascular Differentiation and Development Study Section (CDD)
Program Officer
Galis, Zorina S
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Yale University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
New Haven
State
CT
Country
United States
Zip Code
06510