Amotl2a interacts with the Hippo effector Yap1 and the Wnt/β-catenin effector Lef1 to control tissue size in zebrafish

eLife, Sep 2015

During development, proliferation must be tightly controlled for organs to reach their appropriate size. While the Hippo signaling pathway plays a major role in organ growth control, how it senses and responds to increased cell density is still unclear. Here we use the zebrafish lateral line primordium (LLP), a group of migrating epithelial cells that form sensory organs, to understand how tissue growth is controlled during organ formation. Loss of the cell junction-associated Motin protein Amotl2a leads to overproliferation and bigger LLP, affecting the final pattern of sensory organs. Amotl2a function in the LLP is mediated together by the Hippo pathway effector Yap1 and the Wnt/β-catenin effector Lef1. Our results implicate for the first time the Hippo pathway in size regulation in the LL system. We further provide evidence that the Hippo/Motin interaction is essential to limit tissue size during development.

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Amotl2a interacts with the Hippo effector Yap1 and the Wnt/β-catenin effector Lef1 to control tissue size in zebrafish

Sobhika Agarwala Sandra Duquesne Kun Liu Anton Boehm Lin Grimm Sandra Link Sabine König Stefan Eimer Olaf Ronneberger Virginie Lecaudey This PDF is the version of the article that was accepted for publication after peer review. Fully formatted HTML, PDF, and XML versions will be made available after technical processing, editing, and proofing. - Stay current on the latest in life science and biomedical research from eLife. Sign up for alerts at effector Lef1 to control tissue size in zebrafish Sandra Link1,2, Sabine König1, Stefan Eimer1,4,5, Olaf Ronneberger1,3, Virginie Lecaudey1, 2* 1 BIOSS Centre for Biological Signalling Studies 2 Developmental Biology, Institute for Biology I, Faculty of Biology 3 Image Analysis Lab, Institute for Computer Science 4 ZBSA Center for Biological Systems Analysis 5 Institute for Biology III, Faculty of Biology Albert-Ludwigs-Universität Freiburg, 79104 Freiburg, Germany. * Present Address: Prof. Dr. Virginie Lecaudey Goethe-Universitaet Frankfurt Institute for Cell Biology and Neuroscience Developmental Biology of Vertebrates Max-von-Laue-Strasse 13 D-60438 Frankfurt am Main Phone: +49 (0)69 798 42102 Email: Running title: Amotl2a regulates tissue size in zebrafish Keywords: Amotl2 / Hippo / Wnt/ Proliferation/ Organ size / Yap/ Lef1/ Zebrafish Abstract word count: 141 words Main text word count: 5796 words INTRODUCTION 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 Amotl2a is required to limit the proliferation rate in the trailing region of Nechiporuk AV, Raible DW. 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Available from: 43774&retmode=ref&cmd=prlinks Supplementary figure legends 1) Supplementary tables A, B, C, D related to the Material and Methods section Source data files: 1) Figure 1-source data 1: Relative length of the amotl2a-free (excel sheet 1 2) Figure 2-source data1: Migration speed in amotl2a morphants 3) Figure 3-source data1: Cell counts in amotl2a morphants 4) Figure 3-source data2: Cell counts in rescue experiment of amotl2a morphants 6) Figure 3-source data 4: Cell counts in amotl2a overexpressing embryos 7) Figure 4-source data1: Cell counts in zygotic amotl2a mutants 8) Figure 4-source data2: Number of deposited neuromasts in MZamotl2a 9) Figure 4-source data 3: Migration speed in MZamotl2a mutants 1.4 1.3 1.2 1.1 1 0.9 0.8 0.7 0.6 0.5 1.3 1.2 1.1 1 0.9 0.8 0.7 0.6 0.5 1.4 1.3 1.2 1.1 1 0.9 0.8 0.7 0.6 0.5 0.4 2.2 2 1.8 1.6 1.4 1.2 1 0.8 0.6 0.4 Fukui H , Terai K , Nakajima H , Chiba A , Fukuhara S , Mochizuki N. 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Sobhika Agarwala, Sandra Duquesne, Kun Liu, Anton Boehm, Lin Grimm, Sandra Link, Sabine König, Stefan Eimer, Olaf Ronneberger, Virginie Lecaudey. Amotl2a interacts with the Hippo effector Yap1 and the Wnt/β-catenin effector Lef1 to control tissue size in zebrafish, eLife, 2015, DOI: 10.7554/eLife.08201