Brazil Nut Effect Drives Pattern Formation in Early Mammalian Embryos

Abstract

Since early mammalian embryos lack chemical gradients, the pattern formation mechanism is an open question. During the second cell fate decision of mouse embryos, the inner cell mass (ICM) segregates into topographically regionalized epiblast (EPI) and primitive endoderm (PrE) layers. Here, we report that the cell segregation process coincides with an emerged periodic expansion-contraction vibration of the blastocyst cavity, which induces a phase transition in the ICM compartment to a higher fluidity state. By experiments and modeling, we demonstrate that the spatial segregation of PrE and EPI precursors is mediated by a "Brazil nut effect"-like viscous segregation mechanism in which the vibration of the cavity induces cyclic directional tissue flows in the compartment of the ICM, which drives the separation and asymmetric migration of PrE and EPI precursors through granular segregation biased by different levels of particle adhesivity and sizes. Furthermore, cyclic embryo vibration also regulates the gene expression of PrE and EPI precursors through mechanotransduction by YAP. Our findings unveil a fundamental mechanism for ensuring the robustness of cell segregation and pattern formation, which is driven by the global geometry and mechanical behavior of early embryos.

Sub‐Nanogram Resolution Measurement of Inertial Mass and Density Using Magnetic‐Field‐Guided Bubble Microthruster

“…To showcase the versatility of the BMT method, we aimed to measure the density of embryos. A mouse embryo typically comprises an outer extraembryonic trophectoderm (TE) layer, an inner cell mass (ICM), and a fluid-filled cavity, [55,56] and its density is expected to vary with cell division and cavity expansion during growth. This density variation could offer valuable insights into cell growth/division and composition changes, yet limited data are available.…”