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The cells of a tissue exist in a complex mechanical environment determined by a dynamic interplay between cell-intrinsic components (e.g. cell-cell and cell-matrix adhesions, cytoskeleton) and cell-extrinsic cues (e.g. extracellular matrix, tensile and compressive forces). Within this complex environment, cell division orientation must be carefully controlled in order to shape the tissue, maintain tissue organisation and regulate cell fate. While we know that the mechanical environment can dire ct spindle orientation in single cells in culture, we have very little understanding of how this relates to cells in an intact tissue. Using the Xenopus laevis embryo, this proposal aims to determine how the mechanical environment influences spindle orientation in an intact in vivo tissue, by addressing the following goals: 1. I will determine how spindle orientation in an in vivo epithelium is affected by manipulation of the mechanical environment and characterise the cellular components tha t underlie orientation. 2. I will determine whether tissue tension provides a cue for spindle orientation, by modelling tension in vivo and applying tensile forces to an ex vivo tissue. 3. I will uncover the cellular machinery that links the spindle to the mechanical environment, by investigating spindle-actin, specific molecular motors and by performing a candidate screen.
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