Impaired wound healing in embryonic and adult mice lacking vimentin

It is generally assumed that the vimentin intermediate filament network pre sent in most mesenchymally-derived cells is in part responsible for the str ength and integrity of these cells, and necessary for any tissue movements that require the generation of significant tractional forces, Surprisingly, we have shown that transgenic KO mice deficient for vimentin are apparentl y able to undergo embryonic development absolutely normally and go onto dev elop into adulthood and breed without showing any obvious phenotype, Howeve r, fibroblasts derived from these mice are mechanically weak and severely d isabled in their capacity to migrate and to contract a 3-D collagen network , To assess whether these functions are necessary for more challenging tiss ue movements such as those driving in vivo tissue repair processes, we have analysed wound healing ability in wild-type versus vimentin-deficient embr yos and adult mice, Wounds in vimentin-deficient adult animals showed delay ed migration of fibroblasts into the wound site and subsequently retarded c ontraction that correlated with a delayed appearance of myofibroblasts at t he wound site, Wounds made to vimentin-deficient embryos also failed to hea l during the 24 hour culture period it takes for wild-type embryos to fully heal an equivalent wound, By DiI marking the wound mesenchyme and followin g its fate during the healing process we showed that this impaired healing is almost entirely due to a failure of mesenchymal contraction at the embry onic wound site, These observations reveal an in vivo phenotype for the vim entin-deficient mouse, and challenge the dogma that key morphogenetic event s occurring during development. require generation of significant tractiona l forces by mesenchymal cells.