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YAP is essential for tissue tension to ensure vertebrate 3D body shape.

ABSTRACT: 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 head. Tissue morphogenesis depends on force generation, force transmission through the tissue, and response of tissues and extracellular matrix to force. Although a century ago D'Arcy Thompson postulated that terrestrial animal body shapes are conditioned by gravity, 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.

SUBMITTER: Porazinski S

PROVIDER: S-EPMC4720436 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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YAP is essential for tissue tension to ensure vertebrate 3D body shape.

Porazinski Sean S Wang Huijia H Asaoka Yoichi Y Behrndt Martin M Miyamoto Tatsuo T Morita Hitoshi H Hata Shoji S Sasaki Takashi T Krens S F Gabriel SFG Osada Yumi Y Asaka Satoshi S Momoi Akihiro A Linton Sarah S Miesfeld Joel B JB Link Brian A BA Senga Takeshi T Shimizu Nobuyoshi N Nagase Hideaki H Matsuura Shinya S Bagby Stefan S Kondoh Hisato H Nishina Hiroshi H Heisenberg Carl-Philipp CP Furutani-Seiki Makoto M

Nature 20150316 7551

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 head. Tissue morphogenesis depends on force generation, force transmission through the tissue, and response of tissues and extracellular matrix to force. Although a century ago D'Arcy Thompson postulated that terrestrial animal body shapes are conditioned by gr ...[more]

PMID: 25778702

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Project description:PurposeTotal and regional body composition are important indicators of health and mortality risk, but their measurement is usually restricted to controlled environments in clinical settings with expensive and specialized equipment. A method that approaches the accuracy of the current gold standard method, dual-energy x-ray absorptiometry (DXA), while only requiring input from widely available consumer grade equipment, would enable the measurement of these important biometrics in the wild, enabling data collection at a scale that would have previously been prohibitive in time and expense. We describe an algorithm for predicting three-dimensional (3D) body shape and composition from a single frontal 2-dimensional image acquired with a digital consumer camera.MethodsDuplicate 3D optical scans, two-dimensional (2D) optical images, and DXA whole-body scans were available for 183 men and 233 women from the Shape Up! Adults Study. A principal component analysis vector basis was fit to 3D point clouds of a training subset of 152 men and 194 women. The relationship between this vector space and DXA-derived body composition was modeled with linear regression. The principal component 3D shape was then fitted to match a silhouette extracted from a 2D photograph of a novel body. Body composition was predicted from the resulting 3D shape match using the linear mapping between the principal component parameters and the DXA metrics. Accuracy of body composition estimates from the silhouette method was evaluated against a simple model using height and weight as a baseline, and against DXA measurements as ground truth. Test-retest precision of the silhouette method was evaluated using the duplicate 2D optical images and compared against precision of the duplicate DXA scans. Paired t-tests were performed to detect significant differences between the sets.ResultsResults were reported on a held-out set. Body composition prediction achieved R2 s of 0.81 and 0.74 for percent fat prediction of males and females, respectively, on a held-out test set consisting of 31 males and 39 females. Precision estimates for fat mass were 2.31% and 2.06% for males and females, respectively, compared to 1.26% and 0.68% for DXA scans. The t-tests revealed no statistically significant differences between the silhouette method measurements and DXA measurements, or between retests.ConclusionTotal and regional body composition measures can be estimated from a single frontal photograph of a human body. Body composition prediction using consumer level photography can enable early screening and monitoring of possible physiological indicators of metabolic disease in regions where medical imagery or clinical assessment is inaccessible.

Dataset Information

YAP is essential for tissue tension to ensure vertebrate 3D body shape.

Publications

YAP is essential for tissue tension to ensure vertebrate 3D body shape.

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