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

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


S. F.Gabriel Krens

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 Nagase

Shinya Matsuura

Stefan Bagby

Hisato Kondoh

Hiroshi Nishina

Carl Philipp Heisenberg

Makoto Furutani-Seiki


© 2015 Macmillan Publishers Limited. All rights reserved. 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.


Krens, S. F., Porazinski, S., Wang, H., Asaoka, Y., Behrndt, M., Miyamoto, T., …Furutani-Seiki, M. (2015). YAP is essential for tissue tension to ensure vertebrate 3D body shape. Nature, 521(7551), 217-221.

Journal Article Type Article
Acceptance Date Dec 29, 2014
Online Publication Date Mar 16, 2015
Publication Date May 14, 2015
Journal Nature
Print ISSN 0028-0836
Electronic ISSN 1476-4687
Publisher Nature Research
Peer Reviewed Peer Reviewed
Volume 521
Issue 7551
Pages 217-221
Keywords morphogenesis, 3D body shape, tissue tension, actomyosin network, cell stacking, tissue alignment, fibronectin assembly
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