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The skin epidermis forms mainly by the stratification or differentiation of keratinocytes which dividing begin from the basal region right above the dermis. As the keratinocytes moved outward, they cease dividing and initiate their terminal differentiation process such as enucleation and keratinization. This regeneration and maintenance of the epidermis is dependent on the precise regulation of cellular proliferation, differentiation and apoptosis orchestrated with the underlying dermal tissue. Once the skin integrity is damaged, it is critical to activate the repair process in place to prevent the host from being exposed to foreign particle and infectious agents. The regulation of wound healing is also dictated by epithelial-mesenchymal interactions and purportedly mediated by the action of central players, such as chemokines and growth factors. The synchrony of this interaction is important to prevent excessive or insufficient wound repair. This complex interplay demands the expression of soluble factors exerting autocrine and paracrine activity, and importantly the integration of such diverse signals culminating in appropriate cellular responses. Apart from wound healing, a collective research has also revealed the involvement of stromal fibroblasts in cancer development. It is conceivable that irregularities or aberrations in the epithelial-stromal interaction can either enhance or attenuate tumor cell proliferation and metastasis. Though the importance of the epithelial-mesenchymal communication is well realized, the mechanism underlying this event needs in-depth study. Thus, this study aims to understand the molecular communications between fibroblasts and keratinocytes during skin homeostasis and wound healing. Using a combination of molecular biology techniques, in vitro organotypic cultures and in vivo animal experimentation, we analyze the growth characteristics of normal epithelial cells and the wound microenvironment. A better understanding of the molecular dialogue between fibroblasts and the epithelium opens a new avenue for the development of new therapies for wound treatment. DOCTOR OF PHILOSOPHY (SBS)