title: Anisotropic stress orients remodelling of mammalian limb bud ectoderm.
abstract: The physical forces that drive morphogenesis are not well characterized in vivo, especially among vertebrates. In the early limb bud, dorsal and ventral ectoderm converge to form the apical ectodermal ridge (AER), although the underlying mechanisms are unclear. By live imaging mouse embryos, we show that prospective AER progenitors intercalate at the dorsoventral boundary and that ectoderm remodels by concomitant cell division and neighbour exchange. Mesodermal expansion and ectodermal tension together generate a dorsoventrally biased stress pattern that orients ectodermal remodelling. Polarized distribution of cortical actin reflects this stress pattern in a β-catenin- and Fgfr2-dependent manner. Intercalation of AER progenitors generates a tensile gradient that reorients resolution of multicellular rosettes on adjacent surfaces, a process facilitated by β-catenin-dependent attachment of cortex to membrane. Therefore, feedback between tissue stress pattern and cell intercalations remodels mammalian ectoderm.
authors.affiliation: Program in Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, Toronto M5G 1X8, Canada.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Lau
authors.affiliation: Program in Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, Toronto M5G 1X8, Canada.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Tao
authors.affiliation: 1] Department of Mechanical and Industrial Engineering, University of Toronto, Toronto M5S 3G8, Canada [2] Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto M5S 3G9, Canada.
authors.forename: Haijiao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Mechanical and Industrial Engineering, University of Toronto, Toronto M5S 3G8, Canada.
authors.forename: Jun
authors.initials: J
authors.lastname: Wen
authors.affiliation: Program in Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, Toronto M5G 1X8, Canada.
authors.forename: Kendra
authors.initials: K
authors.lastname: Sturgeon
authors.affiliation: Program in Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, Toronto M5G 1X8, Canada.
authors.forename: Natalie
authors.initials: N
authors.lastname: Sorfazlian
authors.affiliation: 1] Program in Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, Toronto M5G 1X8, Canada [2] Department of Molecular Genetics, University of Toronto, Toronto M5S 1A8, Canada.
authors.forename: Savo
authors.initials: S
authors.lastname: Lazic
authors.affiliation: Program in Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, Toronto M5G 1X8, Canada.
authors.forename: Jeffrey T A
authors.initials: JT
authors.lastname: Burrows
authors.affiliation: 1] Mouse Imaging Centre, Hospital for Sick Children, Toronto Centre for Phenogenomics, Toronto M5T 3H7, Canada [2] Department of Medical Biophysics, University of Toronto, Toronto M5T 3H7, Canada.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Wong
authors.affiliation: 1] Program in Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, Toronto M5G 1X8, Canada [2] Department of Molecular Genetics, University of Toronto, Toronto M5S 1A8, Canada.
authors.forename: Danyi
authors.initials: D
authors.lastname: Li
authors.affiliation: Program in Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, Toronto M5G 1X8, Canada.
authors.forename: Steven
authors.initials: S
authors.lastname: Deimling
authors.affiliation: 1] Program in Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, Toronto M5G 1X8, Canada [2] Department of Molecular Genetics, University of Toronto, Toronto M5S 1A8, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: Ciruna
authors.affiliation: 1] Program in Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, Toronto M5G 1X8, Canada [2] Department of Molecular Genetics, University of Toronto, Toronto M5S 1A8, Canada.
authors.forename: Ian
authors.initials: I
authors.lastname: Scott
authors.affiliation: 1] Department of Mechanical and Industrial Engineering, University of Toronto, Toronto M5S 3G8, Canada [2] Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto M5S 3G9, Canada.
authors.forename: Craig
authors.initials: C
authors.lastname: Simmons
authors.affiliation: 1] Mouse Imaging Centre, Hospital for Sick Children, Toronto Centre for Phenogenomics, Toronto M5T 3H7, Canada [2] Department of Medical Biophysics, University of Toronto, Toronto M5T 3H7, Canada.
authors.forename: R Mark
authors.initials: RM
authors.lastname: Henkelman
authors.affiliation: Program in Molecular Biology, School of Medicine, University of Colorado, Aurora, Colorado 80045, USA.
authors.forename: Trevor
authors.initials: T
authors.lastname: Williams
authors.affiliation: Developmental Biology Program, Sloan-Kettering Institute, New York 10065, USA.
authors.forename: Anna-Katerina
authors.initials: AK
authors.lastname: Hadjantonakis
authors.affiliation: 1] Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto M5S 3G9, Canada [2] Cell and Systems Biology, University of Toronto, Toronto M5G 3G5, Canada.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Fernandez-Gonzalez
authors.affiliation: 1] Department of Mechanical and Industrial Engineering, University of Toronto, Toronto M5S 3G8, Canada [2] Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto M5S 3G9, Canada.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: 1] Program in Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, Toronto M5G 1X8, Canada [2] Department of Molecular Genetics, University of Toronto, Toronto M5S 1A8, Canada [3] Division of Orthopaedic Surgery, Hospital for Sick Children and University of Toronto, Toronto M5G 1X8, Canada.
authors.forename: Sevan
authors.initials: S
authors.lastname: Hopyan
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D016880:Anisotropy; D002450:Cell Communication; D002455:Cell Division; D016764:Cell Polarity; D004475:Ectoderm / Q000378:metabolism / Q000502:physiology*; D046149:Embryo Culture Techniques; D053595:Embryonic Stem Cells / Q000502:physiology; D005246:Feedback; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D018878:Limb Buds / Q000378:metabolism / Q000502:physiology*; D040542:Mechanotransduction, Cellular; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018715:Microscopy, Video; D008954:Models, Biological; D009024:Morphogenesis; D010641:Phenotype; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000378:metabolism; D013314:Stress, Mechanical; D013997:Time Factors; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; C495267:CTNNB1 protein, mouse; D051176:beta Catenin; C496354:Fgfr2 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2