Developmental mechanisms of posterior axis termination in vertebrates - 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.