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YAP is essential for tissue tension to ensure vertebrate 3D body shape. Nature 2015 May 14;521(7551):217-221

Date

03/18/2015

Pubmed ID

25778702

Pubmed Central ID

PMC4720436

DOI

10.1038/nature14215

Scopus ID

2-s2.0-84929315796   132 Citations

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.

Author List

Porazinski S, Wang H, Asaoka Y, Behrndt M, Miyamoto T, Morita H, Hata S, Sasaki T, Krens SFG, Osada Y, Asaka S, Momoi A, Linton S, Miesfeld JB, Link BA, Senga T, Shimizu N, Nagase H, Matsuura S, Bagby S, Kondoh H, Nishina H, Heisenberg CP, Furutani-Seiki M

Author

Brian A. Link PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Actomyosin
Adaptor Proteins, Signal Transducing
Animals
Body Size
Embryo, Nonmammalian
Fish Proteins
GTPase-Activating Proteins
Genes, Essential
Gravitation
Humans
Morphogenesis
Mutation
Organ Size
Oryzias
Phenotype
Protein-Serine-Threonine Kinases
Signal Transduction
Spheroids, Cellular
jenkins-FCD Prod-486 e3098984f26de787f5ecab75090d0a28e7f4f7c0