Homeobox gene Msx-2 is expressed at sites of epithelial-mesenchymal interactions during tissue morphogenesis. We hypothesize that Msx-2 regulates skin morphogenesis during wound repair, which was tested by studying excisional skin wound closure. Isolated keratinocytes and dermal fibroblasts of Msx-2 wild type and knockout mice were also studied to determine the effects of Msx-2. Results showed that Msx-2 mRNA was induced in epidermis and dermis during wound repair. Additionally, Msx-2 knockout mice exhibited enhanced re-epithelialization and faster wound closure than the wild type control. These repair phenotypes may be attributed to keratinocytes motility and fibroblast interaction with collagen matrix as, in vitro, Msx-2 knockout keratinocytes exhibited increased motility, and fibroblasts show stronger collagen matrix contraction and expressed increased levels of alpha2beta1 than wild type control. Msx-2 knockout fibroblasts were refractory to BMP4 in collagen matrix contraction. In conclusion, Msx-2 may regulate skin morphogenesis during repair a both epithelial and mesenchymal levels. |