Species-specific WNT requirements shape somite morphogenesis in mammalian embryo models

Abstract

Somitogenesis establishes the metameric body plan of the vertebrate embryo and can be recapitulated in vitro using stem cell-based embryo models. Although these systems are well established in individual species, they have rarely been compared across species, leaving unresolved how conserved developmental programmes generate species-specific tissue organisation. Here, we compare somitogenesis in embryo models derived from human, pig, sheep and cow pluripotent stem cells and investigate how WNT signalling and the extracellular matrix regulate axis segmentation. Under identical induction conditions, human and pig models diverge in cell-type composition and morphology, revealing distinct modes of axial elongation. Increasing WNT stimulation restores somite formation in pig models but fails to restore ordered segmentation. Furthermore, each of the four mammalian species requires a different level of WNT stimulation and matrix embedding time for somite formation. Finally, comparative analyses identify species-specific differences in progenitor dynamics. Human models, showing ordered segmentation, retain a posterior mesoderm-producing domain, whereas pig models show rapid depletion of this domain, associated with simultaneous somite formation. Together, these findings reveal species-specific requirements for mammalian somitogenesis in stem cell-derived embryo models and suggest that maintenance of a posterior axial domain contributes to ordered segmentation.