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Physical forces involved in collective migration of mesenchymal versus epithelial cells (MESENCHYMAL COLL MOT)
Date du début: 1 juin 2013, Date de fin: 31 mai 2015 PROJET  TERMINÉ 

"Coordinated migration of cells is an important process in development and physiology. Collective migration has been extensively studied in tightly connected cell sheets, or epithelia, with recent studies reporting forces in epithelial collective migration. Although a physical and functional connection between the cells throughout the whole process has been thought necessary for collective migration, collective behaviour has recently been reported in the migration of loosely coherent neural crest (NC) cells. The biomechanical basis of this collective behaviour is poorly understood. NC is a classic example of mesenchymal cells: after undergoing an epithelial-to-mesenchymal-transition (EMT) NC cells migrate long distances as a group in a coordinated and cooperative fashion. Although NC's do not form stable connections, they establish short lived contacts. We will test the hypothesis that these temporary contacts are able to transmit sufficient mechanical forces between the cells to create a collective migration pattern similar to epithelia.We propose to quantitatively describe the collective motion of Xenopus NC cells and the physical forces involved. Mesenchymal behaviour will be compared with the migration of placode and epiderm, two well-known epithelial tissues. We propose to investigate shear and normal stress within the migrating mesenchymal and epithelial groups.Measurements in vitro will include trajectory analysis, traction forces and intercellular forces, using time lapse, force gel and monolayer stress microscopy. In vivo force generation between NC's will be measured in Xenopus and zebrafish embryos using a FRET mechanosensor, trajectory analysis will be performed in Xenopus graft embryos and transgenic zebrafish line expressing nuclear-RFP in NC cells. Based on experimental findings, the role of transient cell-cell adhesions in collective migration will be studied with cell-based modelling."