The protocadherin PAPC establishes segmental boundaries during somitogenesis in Xenopus embryos

Background: One prominent example of segmentation in vertebrate embryos is the subdivision of the paraxial mesoderm into repeating, metameric structur es called somites. During this process, cells in the presomitic mesoderm (P SM) are first patterned into segments leading secondarily to differences re quired for somite morphogenesis such as the formation of segmental boundari es. Recent studies have shown that a segmental pattern is generated in the PSM of Xenopus embryos by genes encoding a Mesp-like bHLH protein called Th ylacine1 and components of the Notch signaling pathway. These genes establi sh a repeating pattern of gene expression that subdivides cells in the PSM into anterior and posterior half segments, but how this pattern of gene exp ression leads to segmental boundaries is unknown. Recently, a member of the protocadherin family of cell adhesion molecules, called PAPC, has been sho wn to be expressed in the PSM of Xenopus embryos in a half segment pattern, suggesting that it could play a role in restricting cell mixing at the ant erior segmental boundary. Results: Here, we examine the expression and function of PAPC during segmen tation of the paraxial mesoderm in Xenopus embryos. We show that Thylacine1 and the Notch pathway establish segment identity one segment prior to the segmental expression of PAPC, Altering segmental identity in embryos by per turbing the activity of Thylacine1 and the Notch pathway, or by treatment w ith a protein synthesis inhibitor, cycloheximide, leads to the predicted ch anges in the segmental expression of PAPC, By disrupting PAPC function in e mbryos using a putative dominant-negative or an activated form of PAPC, we show that segmental PAPC activity is required for proper somite formation a s well as for maintaining segmental gene expression within the PSM. Conclusions: Segmental expression of PAPC is established in the PSM as a do wnstream consequence of segmental patterning by Thylacine1 and the Notch pa thway. We propose that PAPC is part of the mechanism that establishes the s egmental boundaries between posterior and anterior cells in adjacent segmen ts.