Cell surface fluctuations regulate early embryonic lineage sorting

• Published in: Cell Vol. 185; no. 5; pp. 777 - 793.e20
• Main Authors: Yanagida, Ayaka, Corujo-Simon, Elena, Revell, Christopher K., Sahu, Preeti, Stirparo, Giuliano G., Aspalter, Irene M., Winkel, Alex K., Peters, Ruby, De Belly, Henry, Cassani, Davide A.D., Achouri, Sarra, Blumenfeld, Raphael, Franze, Kristian, Hannezo, Edouard, Paluch, Ewa K., Nichols, Jennifer, Chalut, Kevin J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.03.2022; Cell Press
• Subjects: Animals; Blastocyst - metabolism; Cell Differentiation - physiology; Cell Lineage - physiology; Cell Membrane - metabolism; cell sorting; cell surface dynamics; cell surface mechanics; embryo development; Embryo, Mammalian - metabolism; Embryonic Development; Endoderm - metabolism; lineage segregation; Mammals; Mice; morphogenesis; Protein Transport; lineage segregation; cell surface mechanics; embryo development; morphogenesis; cell surface dynamics; cell sorting
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2022.01.022

In development, lineage segregation is coordinated in time and space. An important example is the mammalian inner cell mass, in which the primitive endoderm (PrE, founder of the yolk sac) physically segregates from the epiblast (EPI, founder of the fetus). While the molecular requirements have been well studied, the physical mechanisms determining spatial segregation between EPI and PrE remain elusive. Here, we investigate the mechanical basis of EPI and PrE sorting. We find that rather than the differences in static cell surface mechanical parameters as in classical sorting models, it is the differences in surface fluctuations that robustly ensure physical lineage sorting. These differential surface fluctuations systematically correlate with differential cellular fluidity, which we propose together constitute a non-equilibrium sorting mechanism for EPI and PrE lineages. By combining experiments and modeling, we identify cell surface dynamics as a key factor orchestrating the correct spatial segregation of the founder embryonic lineages. [Display omitted] •EPI and PrE mechanically segregate in early mouse embryos•Segregation is not explained by classical, static mechanical models•Segregation is instead explained by a dynamic parameter, cell surface fluctuations•Fluctuations link to cell fluidity, together comprising a non-equilibrium sorting model In early mammalian embryos differential cell surface fluctuations, rather than static physical parameters, account for the sorting of the primitive endoderm from the epiblast in the inner cell mass.