Role of the miR 221-222 cluster in vascular development

miR 221-222簇在血管发育中的作用

基本信息

项目摘要

DESCRIPTION (provided by applicant): The formation of new blood vessels is required for embryonic development as well as the progression of numerous diseases. The processes that govern blood vessel formation and remodeling are conserved allowing the use model systems to investigate this process. The zebrafish has emerged as an ideal genetic system to dissect the molecular mechanisms involved in vascular development. Furthermore, the transparency of the zebrafish embryos facilitates direct visualization of endothelial cell behaviors in vivo during blood vessel development. Recent work has implicated small non- coding RNAs, referred to as microRNAs, in the proper development of the vascular system. However, little is known about the signaling pathways that miRNAs control during this process. Using deep sequencing methods, I have identified a number of endothelial expressed miRNAs. Furthermore, initial functional characterization of these miRNAs suggests that they play distinct and specific roles in vascular development. In this proposal, I will investigate the role of two endothelial miRNAs, miR-221 and miR-222, by generating zebrafish bearing targeted deletions within miRNA seed sequences using zinc finger nucleases. In parallel, I will generate an endothelial cell-specific transgenic line expressing myc tagged Argonaute 2 (Ago2). This line will allow me to purify miR-221 and miR-222 target complexes specifically from endothelial cells through immunoprecipitation of Ago2. The detailed phenotypic analysis of miRNA-knockout zebrafish, along with the ability to identify relevant endothelial-cell specific miRNA targets will allow me to determine what pathways and cell behaviors miR-221 or miR-222 may be controlling. These findings will then enable me to dissect the genetic networks regulated by endothelial miRNAs during vascular development. Together, the ability to combine targeted genetic manipulation of miRNAs along with the detailed imaging approaches available in the zebrafish, will allow me to gain novel insights onto the role of miRNAs in vascular development. PUBLIC HEALTH RELEVANCE: We are developing technology to facilitate the in vivo study of microRNAs in the vascular system. The resulting data will allow us to gain new knowledge concerning microRNA function in controlling endothelial cell function and blood vessel formation.
描述(由申请人提供):胚胎发育以及多种疾病的进展需要新血管的形成。控制血管形成和重塑的过程是保守的,允许使用模型系统研究此过程。斑马鱼已成为一种理想的遗传系统,用于剖析与血管发育有关的分子机制。此外,斑马鱼胚胎的透明度促进了血管发育过程中体内内皮细胞行为的直接可视化。最近的工作暗示了小型非编码RNA,称为microRNA,在血管系统的适当发展中。但是,对于miRNA在此过程中控制的信号传导途径知之甚少。使用深层测序方法,我已经确定了许多内皮表达的miRNA。此外,这些miRNA的最初功能表征表明它们在血管发育中起独特而特定的作用。在此提案中,我将通过使用锌指核酸酶在miRNA种子序列中产生斑马鱼轴承缺失,研究两个内皮miRNA,miR-221和miR-222的作用。同时,我将生成一个表达MYC标记为Argonaute 2(AGO2)的内皮细胞特异性转基因线。这条线将使我能够通过AGO2的免疫沉淀从内皮细胞中纯化miR-221和miR-222靶复合物。 miRNA敲除斑马鱼的详细表型分析,以及鉴定相关内皮细胞特异性miRNA靶标的能力将使我能够确定哪些途径和细胞行为miR-221或miR-222可以控制。然后,这些发现将使我能够在血管发育过程中剖析内皮miRNA调节的遗传网络。共同将有针对性的miRNA遗传操作以及斑马鱼中可用的详细成像方法相结合的能力将使我能够对miRNA在血管发育中的作用进行新颖的见解。 公共卫生相关性:我们正在开发技术,以促进血管系统中microRNA的体内研究。最终的数据将使我们能够获得有关控制内皮细胞功能和血管形成的新知识。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
miRNAs in endothelial cell signaling: the endomiRNAs.
  • DOI:
    10.1016/j.yexcr.2012.12.009
  • 发表时间:
    2013-05-15
  • 期刊:
  • 影响因子:
    3.7
  • 作者:
    Santoro, Massimo M.;Nicoli, S.
  • 通讯作者:
    Nicoli, S.
Isolation and Culture of Adult Zebrafish Brain-derived Neurospheres.
共 2 条
  • 1
前往

Stefania Nicoli的其他基金

miRNA-regulation at focal adhesions establishes vascular mechanohomeostasis
粘着斑处的 miRNA 调节建立血管机械稳态
  • 批准号:
    10656557
    10656557
  • 财政年份:
    2022
  • 资助金额:
    $ 8.72万
    $ 8.72万
  • 项目类别:
miRNA-regulation at focal adhesions establishes vascular mechanohomeostasis
粘着斑处的 miRNA 调节建立血管机械稳态
  • 批准号:
    10510869
    10510869
  • 财政年份:
    2022
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    $ 8.72万
    $ 8.72万
  • 项目类别:
PPIL4 modulation of Notch links neurovascular malformation to brain aneurism
PPIL4对Notch的调节将神经血管畸形与脑动脉瘤联系起来
  • 批准号:
    10335131
    10335131
  • 财政年份:
    2019
  • 资助金额:
    $ 8.72万
    $ 8.72万
  • 项目类别:
PPIL4 modulation of Notch links neurovascular malformation to brain aneurism
PPIL4对Notch的调节将神经血管畸形与脑动脉瘤联系起来
  • 批准号:
    10094262
    10094262
  • 财政年份:
    2019
  • 资助金额:
    $ 8.72万
    $ 8.72万
  • 项目类别:
PPIL4 modulation of Notch links neurovascular malformation to brain aneurism
PPIL4对Notch的调节将神经血管畸形与脑动脉瘤联系起来
  • 批准号:
    10546468
    10546468
  • 财政年份:
    2019
  • 资助金额:
    $ 8.72万
    $ 8.72万
  • 项目类别:
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
    8903529
  • 财政年份:
    2014
  • 资助金额:
    $ 8.72万
    $ 8.72万
  • 项目类别:
Role of the miR 221-222 cluster in vascular development
miR 221-222簇在血管发育中的作用
  • 批准号:
    8458365
    8458365
  • 财政年份:
    2011
  • 资助金额:
    $ 8.72万
    $ 8.72万
  • 项目类别:
Role of the miR 221-222 cluster in vascular development
miR 221-222簇在血管发育中的作用
  • 批准号:
    8532966
    8532966
  • 财政年份:
    2011
  • 资助金额:
    $ 8.72万
    $ 8.72万
  • 项目类别:
Role of the miR 221-222 cluster in vascular development
miR 221-222簇在血管发育中的作用
  • 批准号:
    8611960
    8611960
  • 财政年份:
    2011
  • 资助金额:
    $ 8.72万
    $ 8.72万
  • 项目类别:

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