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 在脊椎动物胚胎发生过程中，由于后端组织的增加，体轴延长。轴向 尾芽内的祖细胞产生神经和近轴中胚层（PSM）组织， 驱动轴的伸长。在树干伸长过程中，轴向祖细胞的数量随时间增加。 在干细胞向尾细胞过渡后，轴向祖细胞的数量逐渐减少。这允许 体节发生的速度超过尾部的伸长，导致PSM的收缩和轴的终止。的目标 本研究旨在探讨鸡胚后轴终止的分子机制。到 为了理解为什么鸡轴在躯干到尾巴过渡后不久就终止，我将与 在鳄鱼和壁虎胚胎中延长的尾巴伸长。我假设尾巴长度的差异 因为短吻鳄和壁虎维持它们的轴向祖细胞的时间更长，而鸡则过早地失去了它们的轴向祖细胞。 维持其轴向祖细胞的能力。关键信号通路如Wnt、Fgf、RA和GDF11，以及 后部Hox基因的表达和糖酵解可能调节尾部轴向祖细胞池的大小。在 三个目标，我将描述的身份和发展轨迹的鸡，鳄鱼，壁虎尾芽 细胞，功能测试候选人，可能会调节鸡尾终止，并调查的作用， 终止时糖酵解。这项工作将是有益的先天性畸形，造成的缺陷， 轴终止，特别是尾部发育不全和骶尾畸胎瘤。