RRC ID 32791
Author 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.
Title YAP is essential for tissue tension to ensure vertebrate 3D body shape.
Journal Nature
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.
Volume 521(7551)
Pages 217-221
Published 2015-5-14
DOI 10.1038/nature14215
PMID 25778702
PMC PMC4720436
MeSH Actomyosin / metabolism Adaptor Proteins, Signal Transducing / genetics Adaptor Proteins, Signal Transducing / metabolism Animals Body Size / genetics* Embryo, Nonmammalian / anatomy & histology Embryo, Nonmammalian / embryology Embryo, Nonmammalian / metabolism Fish Proteins / genetics Fish Proteins / metabolism* GTPase-Activating Proteins / metabolism Genes, Essential / genetics Gravitation Humans Morphogenesis / genetics* Mutation / genetics Organ Size / genetics Oryzias / anatomy & histology* Oryzias / embryology* Oryzias / genetics Phenotype Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism Signal Transduction Spheroids, Cellular / cytology Spheroids, Cellular / metabolism
IF 42.779
Times Cited 121
Medaka MT374 (hirame) MT364 (fukuwarai) MT830 (OK-Cab) WS339 (K-Kaga)