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Nat Cell Biol. 2015 May;17(5):569-79. doi: 10.1038/ncb3156. Epub 2015 Apr 20.

Anisotropic stress orients remodelling of mammalian limb bud ectoderm.

Author information

1
Program in Developmental and Stem Cell Biology, Research Institute, The Hospital for Sick Children, Toronto M5G 1X8, Canada.
2
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.
3
Department of Mechanical and Industrial Engineering, University of Toronto, Toronto M5S 3G8, Canada.
4
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.
5
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.
6
Program in Molecular Biology, School of Medicine, University of Colorado, Aurora, Colorado 80045, USA.
7
Developmental Biology Program, Sloan-Kettering Institute, New York 10065, USA.
8
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.
9
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.

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.

PMID:
25893915
PMCID:
PMC4955842
DOI:
10.1038/ncb3156
[Indexed for MEDLINE]
Free PMC Article

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