权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Maintenance, germ-layer induction, and patterning of neuromesodermal progenitors

神经中胚层祖细胞的维持、胚层诱导和模式化

基本信息

批准号：
10620438
负责人：
Benjamin L Martin
金额：
$ 6.28万
依托单位：
STATE UNIVERSITY NEW YORK STONY BROOK
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-05 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10620438
关键词：
Affect Anterior Binding Biological Assay Blood Vessels Bone Morphogenetic Proteins Brain Cell Culture Techniques Cell Fate Control Cell Lineage Cell Maintenance Cell Transplantation Cells ChIP-seq Competitive Binding Complement Data Development Dorsal Ectoderm Embryo Embryonic Development Epidermis Fluorescence Genes Germ Layers Goals Growth Head Heat-Shock Response Human Individual Knowledge Laboratories Light Maintenance Mesoderm Mesoderm Cell Methods Microscopy Molecular Mus Muscle Muscle Cells Neurons Outcome Output Paper Pathway interactions Pattern Population Positioning Attribute Process Property Proteins Publishing Regenerative Medicine Regulation Resolution Rest Role Signal Pathway Signal Transduction Signaling Protein Skeletal Muscle Somites Source Specific qualifier value Spinal Cord System Testing Time Tissues Transgenic Organisms Undifferentiated WNT Signaling Pathway Work Zebrafish base beta catenin blastomere structure bone cell motility cell type combinatorial gastrulation genetic manipulation in vivo insight morphogens mutant novel progenitor relating to nervous system stem cell biology stem cells transcription factor transcriptome sequencing transgene expression vertebrate embryos

项目摘要

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 new sox2 and sox3 mutant zebrafish lines and heat-shock inducible sox2 and Wnt signaling transgenic lines to determine how Sox2 and Wnt signaling collaborate to maintain NMPs through regulation of a new class of Wnt/βcat target genes. 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.

在脊椎动物身体形成过程中，首先形成头部，然后形成身体的其余部分逐渐远离头部。神经中胚层祖细胞 (NMP) 群位于胚胎的最后端，促进了后部生长的过程。纳米粒子原肠胚结束后保持胚层可塑性，并有助于脊柱的生长脊髓、体节和血管。 NMPs是身体形成所需的关键细胞，然而，由于它们在胚胎发生中的晚期作用以及它们利用了许多原肠胚形成所必需的基因和信号相同，但它们极难学习。我的实验室开发了利用斑马鱼胚胎在体内操纵 NMP 的方法，结合使用细胞移植和时间遗传操作。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分子促进中胚层和外胚层之间胚层决定的特性。这个提议以我们过去的研究为基础，将检查 NMP 维持的分子控制和图案化。在目标 1 中，我们将使用新的 sox2 和 sox3 突变斑马鱼系的细胞移植和热休克诱导 sox2 和 Wnt 信号转导转基因系，以确定 Sox2 和 Wnt 如何信号传导通过调节一类新的 Wnt/βcat 靶基因协同维持 NMP。在目标 2 中，我们将确定骨形态发生蛋白 (BMP) 通路如何充当形态发生素将中胚层胚层形成不同的细胞类型。这个目标将使用新的方法精确调节个体信号通路激活的强度和持续时间移植的细胞。我们的研究结果将有助于破译一些基本原理脊椎动物身体的形成，并将提供有关干细胞使用的重要信息用于再生医学。