KERATINOCYTE GROWTH-FACTOR IS REQUIRED FOR HAIR DEVELOPMENT BUT NOT FOR WOUND-HEALING

Keratinocyte growth factor (KGF), also known as fibroblast growth fact or 7 (FGF7), is synthesized by skin fibroblasts. However, its mitogeni c activity is on skin keratinocytes, where it is the most potent growt h factor identified thus far. To explore KGF's function in vivo, we us ed embryonic stem cell technology to generate mice lacking KGF. Over t ime, their fur developed a matted appearance, very similar to that of the rough mouse, whose recessive mutation maps at or near the KGF locu s on mouse chromosome 2. In contrast to the recently reported transfor ming growth factor-alpha (TGF-alpha) and FGF5 knockouts, which showed defects in the follicle outer root sheath and the hair growth cycle, r espectively, the hair defect in the KGF knockout seemed to be restrict ed to the cells giving rise to the hair shaft. Thus, we have uncovered a third, and at least partially nonoverlapping, growth factor pathway involved in orchestrating hair follicle growth and/or differentiation . Surprisingly, the absence of KGF resulted in no abnormalities in epi dermal growth or wound healing. This was true even when we engineered double knockout mice, null for both KGF and TGF-alpha, two factors tha t are increased dramatically in the normal wound-healing process. Wher eas we found no evidence of compensatory changes at the mRNA level of wounded knockout mice, these data imply that the regulation of epiderm al growth is complex and involves a number of growth stimulatory facto rs that go beyond what are thought to be the major paracrine and autoc rine growth factors. We suggest that the redundancy in epidermal growt h and wound healing is likely to stem from the vitality of these funct ions to the organism, a feature that is not a consideration for the ha ir follicle.