Diversity supplement for Courtney Tello

考特尼·特洛 (Courtney Tello) 的多元化补充

• 批准号: 10336185
• 负责人: Benjamin L Martin
• 金额: $ 0.57万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-05 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10336185
• 关键词: Blood Vessels; Bone Morphogenetic Proteins; Cell Maintenance; Cell Transplantation; Cells; Ectoderm; Embryo; Embryonic Development; Genes; Germ Layers; Growth; Head; Heat-Shock Response; Individual; Laboratories; Mesoderm; Methods; Molecular; Pathway interactions; Pattern; Population; Process; Property; Regenerative Medicine; Rest; Role; Signal Pathway; Signal Transduction; Skeletal Muscle; Somites; Spinal Cord; Tissues; Transgenic Organisms; WNT Signaling Pathway; Zebrafish; blastomere structure; bone; cell type; gastrulation; genetic manipulation; in vivo; morphogens; mutant; progenitor; stem cells

Project Summary: During the establishment of the vertebrate body, the head forms first and the rest of the body grows progressively away from the head. A population of neuromesodermal progenitor cells (NMPs) located at the posterior-most end of the embryo fuels this process of posterior growth. NMPs maintain germ-layer plasticity after the end of gastrulation, and contribute to the growing spinal cord, somites, and blood vessels. NMPs are critical cells required for the formation of the body, yet due to their late temporal role in embryogenesis and the fact that they utilize many of the same genes and signals that are essential for gastrulation, they have been extremely difficult to study. My laboratory has developed methods using the zebrafish embryo to manipulate NMPs in vivo, using a combination of cell transplantation and temporal genetic manipulations. These methods allowed us to determine the existence of zebrafish NMPs and to define some of the basic molecular properties that facilitate their germ-layer decision between mesoderm and ectoderm. This proposal builds on our past studies and will examine the molecular control of NMP maintenance and patterning. In Aim 1 we will use cell transplantation of a new sox2 mutant zebrafish line and heat-shock inducible sox2 and Wnt signaling transgenic lines to determine how Sox2 and Wnt signaling collaborate to maintain NMPs. In Aim 2, we will determine how the Bone Morphogenetic Protein (BMP) pathway acts as a morphogen to pattern the mesodermal germ layer into distinct cell types. This aim will use new methods to precisely regulate the intensity and duration of signaling pathway activation in individual transplanted cells. The results of our study will help decipher some of the basic underpinnings of vertebrate body formation, and will provide essential information regarding the use of stem cells for regenerative medicine.

项目摘要： 在脊椎动物身体的建立过程中，头部首先形成，身体的其余部分生长 逐渐远离头部。一群神经中胚层祖细胞（NMPs）位于 胚胎的最后端为后面的生长过程提供了燃料。核基质蛋白维持胚层可塑性 在原肠胚形成结束后，有助于脊髓、体节和血管的生长。NMP是 这些细胞是身体形成所需的关键细胞，但由于它们在胚胎发生中的晚期作用， 事实上，他们利用许多相同的基因和信号是必需的原肠胚，他们一直是 非常难研究。我的实验室已经开发出一种方法， NMPs在体内，使用细胞移植和时间遗传操作的组合。这些方法 使我们能够确定斑马鱼核基质蛋白的存在，并定义一些基本的分子特性， 促进它们在中胚层和外胚层之间的胚层决定。这项建议是建立在我们过去的基础上 研究并将检查NMP维持和模式化的分子控制。在目标1中，我们将使用细胞 一种新的sox 2突变斑马鱼系的移植及热休克诱导的sox 2和Wnt信号转导 转基因株系，以确定Sox2和Wnt信号传导如何协作以维持NMP。在目标2中，我们将 确定骨形态发生蛋白（BMP）通路如何作为形态发生素来形成骨形成的模式。 中胚层分化为不同的细胞类型。这一目标将使用新的方法来精确地调节 单个移植细胞中信号传导途径激活的强度和持续时间。我们的研究结果 将有助于破译脊椎动物身体形成的一些基本基础， 关于干细胞用于再生医学的信息。