Fig. 3. Using genetically engineered fibroblasts to elucidate stromal-epithelial interactions in organotypic skin co-cultures. Primary human keratinocytes maintain their stratified and differentiated morphology in 3D organotypic co-cultures regardless of whether dermal fibroblasts included are of human (HDF, A) or mouse (MEF, mouse embryonic fibroblasts, B) origin. Substitution of wild-type mouse fibroblasts with genetically engineered fibroblasts from transgenic animals allows for a detailed analysis of the molecular underpinnings of epithelial stromal interactions. Here, c-jun^-/- (C) and junB^-/- (D) fibroblasts are shown to have hypo- or hyperproliferative effects, respectively, on the morphology of human skin. This study demonstrates the utility of 3D co-culture methodologies in dissecting the molecular determinants of paracrine signaling networks. This figure is summarized from a previously published figure (Szabowski et al., 2000).