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• W1966228205 abstract "D’Arcy Thompson predicted a century ago that animal body shape is conditioned by gravity, but there has been no animal model to study how cellular forces are coordinated to generate body shapes that withstand gravity; the hirame medaka fish mutant, with pronounced body flattening, reveals how the hirame/YAP gene controls gravity-resisting cellular forces to produce complex 3D organs and body shapes. How is tissue tension controlled at the organismal level to maintain body shape and complex three-dimensional structures? Makoto Furutani-Seiki and colleagues describe a medaka fish mutant, hirame (hir), with a flattened body. They show that the phenotype is due to reduction of internal forces caused by the absence of YAP protein, part of the Hippo signalling pathway. This striking effect is linked to the control exerted by YAP on actomyosin-mediated tension through the regulation of the RhoGAP GTPase activating protein ARHGAP18. YAP also controls the 3D structure of human cell spheres in this manner in a human cell culture system. Vertebrates have a unique 3D body shape in which correct tissue and organ shape and alignment are essential for function. For example, vision requires the lens to be centred in the eye cup which must in turn be correctly positioned in the head1. Tissue morphogenesis depends on force generation, force transmission through the tissue, and response of tissues and extracellular matrix to force2,3. Although a century ago D’Arcy Thompson postulated that terrestrial animal body shapes are conditioned by gravity4, there has been no animal model directly demonstrating how the aforementioned mechano-morphogenetic processes are coordinated to generate a body shape that withstands gravity. Here we report a unique medaka fish (Oryzias latipes) mutant, hirame (hir), which is sensitive to deformation by gravity. hir embryos display a markedly flattened body caused by mutation of YAP, a nuclear executor of Hippo signalling that regulates organ size. We show that actomyosin-mediated tissue tension is reduced in hir embryos, leading to tissue flattening and tissue misalignment, both of which contribute to body flattening. By analysing YAP function in 3D spheroids of human cells, we identify the Rho GTPase activating protein ARHGAP18 as an effector of YAP in controlling tissue tension. Together, these findings reveal a previously unrecognised function of YAP in regulating tissue shape and alignment required for proper 3D body shape. Understanding this morphogenetic function of YAP could facilitate the use of embryonic stem cells to generate complex organs requiring correct alignment of multiple tissues." @default.
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• W1966228205 date "2015-03-16" @default.
• W1966228205 modified "2023-10-14" @default.
• W1966228205 title "YAP is essential for tissue tension to ensure vertebrate 3D body shape" @default.
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• W1966228205 doi "https://doi.org/10.1038/nature14215" @default.
• W1966228205 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4720436" @default.
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