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Hydraulic control of mammalian embryo size and cell fate
Journal article   Peer reviewed

Hydraulic control of mammalian embryo size and cell fate

Chii Jou Chan, Maria Costanzo, Teresa Ruiz-Herrero, Gregor Mönke, Ryan J Petrie, Martin Bergert, Alba Diz-Muñoz, L Mahadevan and Takashi Hiiragi
Nature (London), v 571(7763), pp 112-116
Jul 2019
PMID: 31189957

Abstract

Animals Blastocyst - cytology Cell Adhesion Cell Differentiation Cell Division Cell Lineage Cell Shape Embryo, Mammalian - anatomy & histology Embryo, Mammalian - cytology Embryo, Mammalian - embryology Embryonic Development Female Male Mechanotransduction, Cellular - physiology Mice Mice, Inbred C3H Mice, Inbred C57BL Tight Junctions Vinculin - metabolism
Size control is fundamental in tissue development and homeostasis . Although the role of cell proliferation in these processes has been widely studied, the mechanisms that control embryo size-and how these mechanisms affect cell fate-remain unknown. Here we use the mouse blastocyst as a model to unravel a key role of fluid-filled lumen in the control of embryo size and specification of cell fate. We find that there is a twofold increase in lumenal pressure during blastocyst development, which translates into a concomitant increase in cell cortical tension and tissue stiffness of the trophectoderm that lines the lumen. Increased cortical tension leads to vinculin mechanosensing and maturation of functional tight junctions, which establishes a positive feedback loop to accommodate lumen growth. When the cortical tension reaches a critical threshold, cell-cell adhesion cannot be sustained during mitotic entry, which leads to trophectoderm rupture and blastocyst collapse. A simple theory of hydraulically gated oscillations recapitulates the observed dynamics of size oscillations, and predicts the scaling of embryo size with tissue volume. This theory further predicts that disrupted tight junctions or increased tissue stiffness lead to a smaller embryo size, which we verified by biophysical, embryological, pharmacological and genetic perturbations. Changes in lumenal pressure and size can influence the cell division pattern of the trophectoderm, and thereby affect cell allocation and fate. Our study reveals how lumenal pressure and tissue mechanics control embryo size at the tissue scale, which is coupled to cell position and fate at the cellular scale.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Cell Biology
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