Hydraulic Control of Mammalian Embryo Size and Cell Fate
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Chan, Chii Jou
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CitationChan, Chii Jou, Maria Costanzo, Teresa Ruiz-Herrero, Gregor Mönke, Ryan J Petrie, Martin Bergert, Alba Diz-Muñoz, L. Mahadevan, and Takashi Hiiragi. 2019. Hydraulic Control of Mammalian Embryo Size and Cell Fate. Nature 571, no. 7763: 112-16.
AbstractSize control is fundamental in tissue development and homeostasis1,2. While the role of cell proliferation in these processes has been widely studied, the mechanisms of embryo size control and how it impacts cell fates remain elusive. Here, we use mouse blastocyst as a model to unravel a key role of fluid-filled lumen in embryo size control and cell fate specification. We find that during blastocyst development, there is a two-fold increase in the lumenal pressure that translates into a concomitant increase in the cell cortical tension and tissue stiffness of trophectoderm (TE) lining the lumen. Increased cortical tension leads to vinculin mechanosensing and maturation of functional tight junctions, thereby establishing 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 TE rupture and blastocyst collapse. A simple theory of hydraulically-gated oscillations recapitulates the dynamics of size oscillations and predicts the scaling of embryo size with tissue volume. The theory further predicts that disrupted tight junctions or increased tissue stiffness lead to smaller embryo size, which we verified by biophysical, embryological, pharmacological and genetic perturbations. Remarkably, changes in lumenal pressure and size can influence TE cell division pattern, thereby impacting cell allocation and fate. Overall, our study reveals how lumenal pressure and tissue mechanics control embryo size at the tissue scale, that in turn couples to cell position and fate at the cellular scale.
Citable link to this pagehttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37374237
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