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

Sean Porazinski, Huijia Wang, Yoichi Asaoka, Martin Behrndt, Tatsuo Miyamoto, Hitoshi Morita, Shoji Hata, Takashi Sasaki, S. F Gabriel Krens, Yumi Osada, Satoshi Asaka, Akihiro Momoi, Sarah Linton, Joel B. Miesfeld, Brian A. Link, Takeshi Senga, Atahualpa Castillo-Morales, Araxi O. Urrutia, Nobuyoshi Shimizu, Hideaki NagaseShinya Matsuura, Stefan Bagby, Hisato Kondoh, Hiroshi Nishina, Carl Philipp Heisenberg, Makoto Furutani-Seiki

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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.

Original languageEnglish
Pages (from-to)217-221
Number of pages5
JournalNature
Volume521
Issue number7551
Early online date16 Mar 2015
DOIs
Publication statusPublished - 14 May 2015

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Porazinski, S., Wang, H., Asaoka, Y., Behrndt, M., Miyamoto, T., Morita, H., ... Furutani-Seiki, M. (2015). YAP is essential for tissue tension to ensure vertebrate 3D body shape. Nature, 521(7551), 217-221. https://doi.org/10.1038/nature14215