PT - JOURNAL ARTICLE AU - Ali Hashmi AU - Sham Tlili AU - Pierre Perrin AU - Alfonso Martinez-Arias AU - Pierre-François Lenne TI - Cell-state transitions and collective cell movement generate an endoderm-like region in gastruloids AID - 10.1101/2020.05.21.105551 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.05.21.105551 4099 - http://biorxiv.org/content/early/2020/06/10/2020.05.21.105551.short 4100 - http://biorxiv.org/content/early/2020/06/10/2020.05.21.105551.full AB - Shaping the animal body plan is a complex process that involves the spatial organization and patterning of different cell layers. Recent advances in live imaging have started to unravel the cellular choreography underlying this process in mammals, however, the sequence of events transforming an unpatterned cell ensemble into structured territories is largely unknown. Here, using 3D aggregates of mouse embryonic stem cells, we study the formation of one of the three germ layers, the endoderm. We show that the endoderm is generated from an epiblast-like state by a three-step mechanism: a release of islands of Ecadherin expressing cells, their flow toward the aggregate tip, and their segregation. Unlike the prevailing view, this mechanism does not require epithelial-to-mesenchymal transitions and vice-versa but rather a fragmentation, which is mediated by Wnt/β-catenin, and a sorting process. Our data emphasize the role of signaling and cell flows in the establishment of the body plan.Competing Interest StatementThe authors have declared no competing interest.