TY - JOUR AU - Lau, Kimberly AU - Tao, Hirotaka AU - Liu, Haijiao AU - Wen, Jun AU - Sturgeon, Kendra AU - Sorfazlian, Natalie AU - Lazic, Savo AU - Burrows, Jeffrey T. A. AU - Wong, Michael D. AU - Li, Danyi AU - Deimling, Steven AU - Ciruna, Brian AU - Scott, Ian AU - Simmons, Craig AU - Henkelman, R. Mark AU - Williams, Trevor AU - Hadjantonakis, Anna-Katerina AU - Fernandez-Gonzalez, Rodrigo AU - Sun, Yu AU - Hopyan, Sevan TI - Anisotropic stress orients remodelling of mammalian limb bud ectoderm JA - Nat Cell Biol PY - 2015/05//print VL - 17 IS - 5 SP - 569 EP - 579 PB - Nature Publishing Group SN - 1465-7392 UR - http://dx.doi.org/10.1038/ncb3156 L3 - 10.1038/ncb3156 M3 - Article L3 - http://www.nature.com/ncb/journal/v17/n5/abs/ncb3156.html#supplementary-information AB - 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 [beta]-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 [beta]-catenin-dependent attachment of cortex to membrane. Therefore, feedback between tissue stress pattern and cell intercalations remodels mammalian ectoderm. ER -