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

• Published in: Mechanisms of development Vol. 94; no. 1; pp. 67 - 78
• Main Authors: Kunisada, Takahiro, Yamazaki, Hidetoshi, Hirobe, Tomohisa, Kamei, Shuichi, Omoteno, Mitsuaki, Tagaya, Hisashi, Hemmi, Hiroaki, Koshimizu, Uichi, Nakamura, Toshikazu, Hayashi, Shin-Ichi
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.06.2000
• Subjects: Animals; Animals, Newborn; c-met; Cadherins - genetics; Cadherins - metabolism; Cytokeratin 14 promoter; E-cadherin; Ear, External; Gene Expression Regulation, Developmental; Hepatocyte growth factor; Hepatocyte Growth Factor - genetics; Hepatocyte Growth Factor - metabolism; Intramolecular Oxidoreductases - metabolism; Keratinocytes - physiology; Keratins - genetics; Melanocyte; Melanocytes - pathology; Melanocytes - physiology; Melanocytosis; Mice; Mice, Transgenic; Promoter Regions, Genetic; Proto-Oncogene Proteins c-kit - metabolism; Proto-Oncogene Proteins c-met - metabolism; Skin - embryology; Skin - growth & development; Skin - pathology; Skin Diseases - genetics; Skin Diseases - pathology; Skin Pigmentation - genetics; Stem Cell Factor - metabolism; Transgenic mouse; TRP-2; TRP-2; Hepatocyte growth factor; Melanocyte; Cytokeratin 14 promoter; Transgenic mouse; c-met; Melanocytosis; E-cadherin
• ISSN: 0925-4773; 1872-6356
• DOI: 10.1016/S0925-4773(00)00308-7

Using the epidermis-specific cytokeratin 14 promoter to deliver HGF exclusively from epidermal keratinocytes, we have examined the potential of hepatocyte growth factor (HGF) secreted from the normal environment to control morphogenesis. The transgenic mice displayed a significant increase of the number 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 the entire life of the mice. Thus, HGF acts as a paracrine agent to promote survival, proliferation and differentiation of melanocyte precursors in vivo, and eventually causes melanocytosis. Loss of E-cadherin expression in dermal melanocyte precursors suggests that HGF caused dermal localization of melanocytes and their precursors by down-regulation of E-cadherin molecules.