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： 在建立脊椎动物的过程中，头部首先形成，其余的身体成长 逐渐远离头部。位于 胚胎的后端最终为后验生长带来了这种过程。 NMP保持菌丝塑性 胃结束后，并有助于生长的脊髓，节点和血管。 NMP是 临界细胞形成人体所需的临界细胞，但由于它们在胚胎发生和 他们利用了许多对胃肠道必不可少的基因和信号的事实，它们一直是 非常困难。我的实验室已经开发了使用斑马鱼胚胎操纵的方法 NMP在体内，结合细胞移植和时间遗传操作的组合。这些方法 允许我们确定斑马鱼NMP的存在并定义一些基本分子特性 这有助于他们在中胚层和外胚层之间的细菌层决定。这项建议建立在我们的过去 研究并将检查NMP维持和模式的分子控制。在AIM 1中，我们将使用单元格 新的Sox2突变体斑马鱼线和热震诱导Sox2和Wnt信号传导的移植 转基因线以确定Sox2和Wnt信号如何协作以维护NMP。在AIM 2中，我们将 确定骨形态发生蛋白（BMP）途径如何充当形态学 中胚层生殖层分为不同的细胞类型。此目标将使用新方法来精确调节 单个移植细胞中信号通路激活的强度和持续时间。我们研究的结果 将有助于破译脊椎动物身体形成的一些基本基础，并将提供必需品 有关使用干细胞用于再生医学的信息。