Cell surface fluctuations regulate early embryonic lineage sorting.

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Yanagida, Ayaka 
Corujo-Simon, Elena 
Revell, Christopher K 
Sahu, Preeti 
Stirparo, Giuliano G 

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.

cell sorting, cell surface dynamics, cell surface mechanics, embryo development, lineage segregation, morphogenesis, Animals, Blastocyst, Cell Differentiation, Cell Lineage, Cell Membrane, Embryo, Mammalian, Embryonic Development, Endoderm, Mammals, Mice, Protein Transport
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Elsevier BV
Wellcome Trust (203151/Z/16/Z)
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (641639)
European Research Council (772798)
European Research Council (772426)
European Research Council (820188)
BBSRC (BB/T007044/1)
Medical Research Council (MC_PC_17230)
Biotechnology and Biological Sciences Research Council (BB/P003575/1)
Medical Research Council (MC_UU_00012/5)
European Research Council (311637)
Biotechnology and Biological Sciences Research Council (BB/T007044/2)