Developmental mechanisms of posterior axis termination in vertebrates

脊椎动物后轴终止的发育机制

• 批准号: 10410356
• 负责人: REBECCA M IZEN
• 金额: $ 4万
• 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/10410356
• 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; Lead; Length; Maintenance; Measures; Metabolic; Metabolic Pathway; Molecular; Mus; Paraxial Mesoderm; Pathway interactions; Phylogeny; Population; Primitive Streaks; Production; Role; Signal Pathway; Signal Transduction; Tail; Teratoma; Testing; Time; Tissues; Transplantation; Vertebrates; WNT Signaling Pathway; Work; Zebrafish; aerobic glycolysis; cell motility; gastrulation; induced pluripotent stem cell; pluripotency; premature; progenitor; relating to nervous system; 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，体轴伸长。轴向 尾芽内的祖细胞产生神经和近轴中胚层 (PSM) 组织，并产生 PSM 轴的驱动伸长。在躯干伸长过程中，轴向祖细胞的数量随着时间的推移而增加。 随着躯干到尾部的转变，轴向祖细胞的数量逐渐减少。这允许 体节发生超过尾部伸长，导致 PSM 收缩和轴终止。目标是 该提案旨在表征鸡胚胎后轴终止的分子机制。到 了解为什么鸡轴在躯干到尾部过渡后不久终止，我将与 鳄鱼和壁虎胚胎中尾巴延长。我假设尾长存在差异 因为短吻鳄和壁虎的轴向祖细胞维持时间更长，而鸡则过早地失去了轴向祖细胞。 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 Hox 基因和糖酵解的表达，可能调节尾部轴向祖细胞库的大小。在 三个目标，我将刻画鸡、鳄鱼、壁虎尾芽的身份和发育轨迹 细胞，功能测试可能调节鸡尾巴终止的候选者，并研究 糖酵解终止。这项工作将为因缺陷而导致的先天畸形提供信息。 轴终止，特别是尾部发育不全和骶尾部畸胎瘤。