Diversity supplement for Courtney Tello

项目总结： 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 胚胎的最后端为后部生长过程提供动力。NMPS维持胚层可塑性 原肠发育结束后，促进脊髓、体节和血管的生长。NMP是 身体形成所需的关键细胞，但由于它们在胚胎发育和胚胎发育中的时间作用较晚 事实上，它们利用了许多相同的基因和信号，这些基因和信号是原肠形成所必需的，它们一直 学习起来极其困难。我的实验室已经开发出使用斑马鱼胚胎来操纵 活体内的NMPS，使用细胞移植和临时遗传操作的组合。这些方法 使我们能够确定斑马鱼NMP的存在，并定义一些基本的分子性质 这有助于它们在中胚层和外胚层之间进行胚层决定。这项建议是建立在我们过去的基础上的 研究并将研究NMP维持和构图的分子控制。在目标1中我们将使用单元格 新的Sox2突变斑马鱼品系的移植及热休克诱导的Sox2和Wnt信号转导 转基因株系，以确定Sox2和Wnt信号如何协作维持NMP。在目标2中，我们将 确定骨形态发生蛋白(BMP)途径如何作为形态生成剂来塑造 中胚层胚层形成不同的细胞类型。这一目标将使用新的方法来精确地规范 单个移植细胞中信号通路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，并将提供必要的 关于干细胞用于再生医学的信息。

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.