Notch coordinates self-organization of germ layers and axial polarity in sea anemone gastruloids

Reaggregated early gastrula cells ("gastruloids") of the sea anemone Nematostella vectensis are able to regenerate into whole polyps within a few days. However, the cellular and molecular mechanisms underlying restoration of body axis and germ layers remains largely unknown. Here, we show that mesodermal cells sort to the periphery of the gastruloid, where they form cell clusters with hitchhiking endodermal cells. One of these clusters immigrates at one pole, forming the future pharynx and inner layer. This morphogenetic behavior that enables the symmetry break of the organizer tissue, requires a Wnt-Notch signaling feedback loop. This highlights a hitherto unknown role of Notch signaling in self-organizing gastruloids. Conservation of Notch-mediated boundary formation between germ layers mirrors similar mechanisms in bilaterians. This demonstrates how adoption of ancestral regulatory networks enables a morphospace converging to similar body plans, thus contributing to evolutionary robustness.