Developmental mechanisms of posterior axis termination in vertebrates

脊椎动物后轴终止的发育机制

• 批准号: 10619586
• 负责人: REBECCA M IZEN
• 金额: $ 3.55万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10619586
• 关键词: Alligators; Anterior; Automobile Driving; Biological Assay; Candidate Disease Gene; Cell division; Cells; Chick Embryo; Chickens; Congenital Abnormality; Defect; Development; Electroporation; Embryo; Embryonic Development; Epiblast; Fibroblast Growth Factor; GDF11 gene; Gene Expression; Genes; Glycolysis; Goals; Head; Histologic; Histology; Homeobox Genes; Human; In Situ Hybridization; Length; Maintenance; Measures; Metabolic; Metabolic Pathway; Molecular; Mus; Paraxial Mesoderm; Pathway interactions; Phylogeny; Population; Primitive Streaks; Production; Proliferating; Repression; Role; Signal Pathway; Signal Transduction; Tail; Teratoma; Testing; Time; Tissues; Transplantation; Vertebrates; WNT Signaling Pathway; Work; Zebrafish; aerobic glycolysis; candidate identification; cell motility; gastrulation; induced pluripotent stem cell; neural; pluripotency; premature; progenitor; single cell sequencing; single-cell RNA sequencing; transcription factor; transcriptome sequencing; vertebrate embryos

Developmental Mechanisms of Posterior Axis Termination in Vertebrates During vertebrate embryogenesis, the body axis elongates due to addition of tissue at the posterior end. Axial progenitors within the tail bud give rise to neural and paraxial mesoderm (PSM) tissues, with production of PSM driving elongation of the axis. During elongation of the trunk, axial progenitors increase in number over time. Following the trunk-to-tail transition, axial progenitors progressively decrease in number. This allows somitigenesis outpace tail elongation, leading to shrinkage of the PSM and termination of the axis. The goal of this proposal is to characterize the molecular mechanism of posterior axis termination in the chicken embryo. To understand why the chicken axis terminates shortly after the trunk-to-tail transition, I will make comparisons with the prolonged tail elongation in alligator and gecko embryos. I hypothesize that tail length differences arise because alligator and geckos maintain their axial progenitors for longer, while chickens prematurely lose the ability to maintain their axial progenitors. Key signaling pathways such as Wnt, Fgf, RA, and GDF11, as well as expression of posterior Hox genes and glycolysis, may regulate the size of the axial progenitor pool in the tail. In three aims, I will characterize the identity and developmental trajectory of chicken, alligator, and gecko tail bud cells, functionally test candidates that may regulate tail termination in chicken, and investigate the role of glycolysis in termination. This work will be informative for congenital malformations that result from defects in axis termination, particularly caudal agenesis and sacrococcygeal teratoma.

脊椎动物后轴终止的发育机制 在脊椎动物的胚胎发生过程中，由于在后端添加组织，体轴会伸长。轴向 尾芽中的祖细胞产生神经和近似中胚层（PSM）组织，并产生PSM 驱动轴的伸长。在树干的伸长过程中，轴向祖细胞的数量随时间增加。 遵循躯干到尾巴过渡，轴向祖细胞的数量逐渐减少。这允许 体积的尾巴延伸，导致PSM的收缩和轴终止。目标 该建议是表征鸡胚胎中轴后终止的分子机制。到 理解为什么鸡轴在后备箱到尾巴过渡后不久终止，我将与 鳄鱼和壁虎胚胎中延长的尾部伸长。我假设尾巴长度差异 因为鳄鱼和壁虎保持其轴向祖细胞更长的时间，而鸡过早地失去了 保持其轴向祖细胞的能力。关键信号通路，例如Wnt，FGF，RA和GDF11以及 后HOX基因和糖酵解的表达可能调节尾部轴向祖细胞池的大小。在 三个目标，我将表征鸡肉，鳄鱼和壁虎尾巴的身份和发育轨迹 细胞，在功能上测试可能调节鸡尾终止的候选者，并研究 终止中的糖酵解。这项工作将使缺陷导致的先天性畸形有关 轴线终止，特别是尾骨发育不全和sacococcygeal畸胎瘤。