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

• 批准号: 10416097
• 负责人: Benjamin L Martin
• 金额: $ 6.85万
• 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/10416097
• 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

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.

在脊椎动物身体的形成过程中，首先形成头部，然后是身体的其余部分