Diverse routes towards early somites in the mouse embryo

Somite formation is foundational to creating the vertebrate segmental body plan. Here, we describe three trajectories towards somite formation in the early mouse embryo. Precursors of the anterior-most somites ingress through the primitive streak before E7 and migrate anteriorly by E7.5, while a second wave of more posterior somites develops in the vicinity of the streak.
Finally, neuromesodermal progenitors (NMPs) are set aside for subsequent trunk somitogenesis. Single-cell profiling of T-/- chimaeric embryos shows that the anterior somites develop in the
absence of T, and suggests a cell-autonomous function of T as a gatekeeper between paraxial mesoderm production and building of the NMP pool. Moreover, we identify putative regulators of early T-independent somites, and challenge the T-Sox2 cross-antagonism model in early NMPs. Our study highlights the concept of molecular flexibility during early cell type specification, with broad relevance for pluripotent stem cell differentiation and disease modelling.