Developmental mechanisms of posterior axis termination in vertebrates

脊椎动物后轴终止的发育机制 在脊椎动物胚胎发育过程中，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旁轴中胚层(PSM)组织，并产生PSM 驱动轴的伸长。在树干伸长期间，轴向祖细胞的数量随着时间的推移而增加。 在躯干到尾巴的转变之后，轴向祖细胞的数量逐渐减少。这使得 体细胞发生超过尾部伸长，导致PSM收缩和轴端终止。的目标是 本研究旨在探讨鸡胚胎后轴终止的分子机制。至 理解为什么鸡轴在躯干到尾巴转换后不久就终止了，我将与 鳄鱼和壁虎胚胎中延长的尾巴长度。我假设会出现尾长差异 因为鳄鱼和壁虎保持它们的轴向祖细胞的时间更长，而鸡过早地失去了 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……里面 三个目标，我将描述鸡、鳄鱼和壁虎尾芽的身份和发育轨迹 细胞，从功能上测试可能调节鸡尾巴终止的候选细胞，并研究 终止时的糖酵解。这项工作将为先天性畸形提供信息，这些先天畸形是由 枢椎终止，特别是尾部发育不全和尾部畸胎瘤。

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.