Linking neurogenesis and vascular stabilization through miRNA dependent pathways

通过 miRNA 依赖性途径将神经发生和血管稳定联系起来

• 批准号: 8903529
• 负责人: Stefania Nicoli
• 金额: $ 41.62万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8903529
• 关键词: 3' Untranslated Regions; Address; Affect; Alzheimer' s Disease; Apoptosis; Applications Grants; Binding; Biogenesis; Blood - brain barrier anatomy; Blood Vessels; Brain; Cells; Central Nervous System Diseases; Cerebral cortex; Data; Defect; Development; Diabetes Mellitus; Disease; Edema; Embryo; Embryonic Development; Endothelial Cells; Etiology; Event; Extravasation; Fishes; Functional RNA; Functional disorder; Future; Gene Expression; Gene Targeting; Genes; Genetic; Glioma; Grant; Health; Hippocampus (Brain); Homeostasis; Human; In Vitro; Inflammation; Intercellular Junctions; Intracranial Hemorrhages; Ischemic Stroke; Label; Lead; Link; MicroRNAs; Modeling; Molecular; Molecular Weight; Mus; Nature; Neuraxis; Neurodegenerative Disorders; Neuronal Differentiation; Neurons; Parkinson Disease; Pathology; Pathway interactions; Permeability; Pharmaceutical Preparations; Proteins; Regulation; Role; Signal Pathway; Signal Transduction; Small RNA; Staging; Stem cells; Testing; Tight Junctions; Time; Tissues; Toxin; Tracer; Transgenic Organisms; Vascular Permeabilities; Zebrafish; cadherin 5; in vivo; loss of function; mutant; nerve stem cell; neurogenesis; novel; pathogen; relating to nervous system; research study; response

DESCRIPTION (provided by applicant): 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.

描述（由申请方提供）：胚胎发育期间血管系统和中枢神经系统之间的相互作用对于血脑屏障（BBB）的形成至关重要。随着内皮细胞在神经组织中发芽，它们失去了开窗并获得了诸如紧密连接的关键特征。血脑屏障维持关键的脑内稳态，限制毒素、药物和病原体进入脑。在本提案中，我们希望分析将神经发生与血管和BBB成熟联系起来的依赖于miR-107的信号通路。我们建议研究1）神经干细胞及其数量如何影响BBB稳定; 2）为什么神经miR-107阳性细胞是血管通透性所必需的; 3）最后影响神经血管稳态的miR-107下游信号通路。我们认为miR-107是一种新的神经miRNA，是正常神经发生和血管稳定所必需的。有趣的是，miR- 107已被指定为糖尿病和其他神经退行性疾病的潜在治疗靶点。因此，我们认为，这项资助中提出的研究对于评估未来miR-107疗法的利弊是必要的。

项目成果

MicroRNAs Establish Uniform Traits during the Architecture of Vertebrate Embryos.

• DOI: 10.1016/j.devcel.2017.02.021
• 发表时间: 2017-03-27
• 期刊: Developmental cell
• 影响因子: 11.8
• 作者: Kasper DM;Moro A;Ristori E;Narayanan A;Hill-Teran G;Fleming E;Moreno-Mateos M;Vejnar CE;Zhang J;Lee D;Gu M;Gerstein M;Giraldez A;Nicoli S
• 通讯作者: Nicoli S