Opposing Nodal and Wnt signalling activities govern the emergence of the mammalian body plan

Abstract

Summary Nodal and Wnt signalling play an important role in the emergence of the mammalian body plan, primarily by orchestrating gastrulation. While the literature suggests they cooperate to build the primitive streak, their individual contributions remain poorly understood. Using gastruloids, we found that Wnt/β-catenin drives a genetic program characteristic of the late primitive streak, promoting the development of posterior body structures in a time and dose-dependent manner. Conversely, Nodal activates a distinct transcriptional module resembling the early streak. By engineering gastruloids with varying levels of Nodal signalling, we demonstrate that a decreasing temporal gradient of Nodal activity is critical for establishing the anterior body, with higher Nodal levels producing more anterior structures in a concentration-dependent manner. Our findings suggest that Nodal and Wnt act antagonistically, initiating distinct developmental modules within the primitive streak. This antagonism is likely the core mechanism driving the early body plan in mammals.