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

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 nu...

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Bibliographic Details
Published in:Mechanisms of development 2000-06, Vol.94 (1), p.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: Article
Language:English
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
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Description
Summary: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.
ISSN:0925-4773
1872-6356
DOI:10.1016/S0925-4773(00)00308-7