Fig. 3.

EMT under confinement and optimal conditions for single and collective migration.

A, a. Classic model of linear EMT. (A) A sub-population of cells within an epithelia loss apicobasal polarity, undergos a switch in their cadherin content at AJs, became individual, and acquires mesenchymal migratory capabilities. When migrating in vivo, these cells are challenged by the physical strains of their surroundings. (a) The diagram shows the high degree of fluidity that a single cell reaches when migrating in confined spaces. Note that although the nucleus limits the degree of deformation that a cell can undergo, it can also deform to allow migration. (B) Schematic representation showing that for single cell migration (SCM) to occurs, cells require to acquire high degree of fluidity, which is very likely to be achieved by the extreme reduction in type-I AJs suffered during EMT. This EMT has to be highly regulated in order to maintain this low type-I cadherin levels and very importantly fluidity. Collective cell migration instead occurs just in optimal conditions of adhesion, fluidity, and EMT. In the absence of EMT an epithelial tissue has high strength of cell-cell adhesion and with that very low fluidity. If EMT is rather mild, this epithelium will maintain its epithelial behaviour with strong cell-cell adhesion mediated by type-I cadherins, this will help this tissue to resist deformation and open space to migrate in physically challenging environments (observed in wound healing or Drosophila border cell migration for instance). If the EMT rate increase, either by increasing the rate of cadherin turnover or using stronger transcriptional regulatory programs, cell clusters migrate as more fluid units that can deform in order to migrate in confined spaces (Neural crest or pLLP for instance). If the fluidity goes to a maximum, confinement and mutual attraction can help low adhesive forces to maintain collectiveness of the migratory group.