Keratinocyte expression of transgenic hepatocyte growth factor affects melanocyte development, leading to dermal melanocytosis

Using the epidermis-specific cytokeratin 14 promoter to deliver HGF exclusi vely from epidermal keratinocytes, we have examined the potential of hepato cyte growth factor (HGF) secreted from the normal environment to control mo rphogenesis. The transgenic mice displayed a significant increase of the nu mber of melanocytes and their precursors in embryos starting not later than 16.5 dpc, and then after birth an explosive increase of dermal melanocytes started within 1 week, and these melanocytes were maintained throughout th e entire life of the mice. Thus, HGF acts as a paracrine agent to promote s urvival, proliferation and differentiation of melanocyte precursors in vivo , and eventually causes melanocytosis. Loss of E-cadherin expression in der mal melanocyte precursors suggests that HGF caused dermal localization of m elanocytes and their precursors by down-regulation of E-cadherin molecules. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.