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First published online 24 June 2009
doi: 10.1242/dev.037168


Development 136, 2511-2521 (2009)
Published by The Company of Biologists 2009


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Two distinct types of mouse melanocyte: differential signaling requirement for the maintenance of non-cutaneous and dermal versus epidermal melanocytes

Hitomi Aoki1, Yasuhiro Yamada2, Akira Hara2 and Takahiro Kunisada1,*

1 Department of Tissue and Organ Development, Regeneration, and Advanced Medical Science, Gifu University Graduate School of Medicine, 1-1, Yanagido, Gifu 501-1194, Japan.
2 Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1-1, Yanagido, Gifu 501-1194, Japan.

* Author for correspondence (e-mail: tkunisad{at}gifu-u.ac.jp)

Accepted 21 May 2009

Unlike the thoroughly investigated melanocyte population in the hair follicle of the epidermis, the growth and differentiation requirements of the melanocytes in the eye, harderian gland and inner ear - the so-called non-cutaneous melanocytes - remain unclear. In this study, we investigated the in vitro and in vivo effects of the factors that regulate melanocyte development on the stem cells or the precursors of these non-cutaneous melanocytes. In general, a reduction in KIT receptor tyrosine kinase signaling leads to disordered melanocyte development. However, melanocytes in the eye, ear and harderian gland were revealed to be less sensitive to KIT signaling than cutaneous melanocytes. Instead, melanocytes in the eye and harderian gland were stimulated more effectively by endothelin 3 (ET3) or hepatocyte growth factor (HGF) signals than by KIT signaling, and the precursors of these melanocytes expressed the lowest amount of KIT. The growth and differentiation of these non-cutaneous melanocytes were specifically inhibited by antagonists for ET3 and HGF. In transgenic mice induced to express ET3 or HGF in their skin and epithelial tissues from human cytokeratin 14 promoters, the survival and differentiation of non-cutaneous and dermal melanocytes, but not epidermal melanocytes, were enhanced, apparently irrespective of KIT signaling. These results provide a molecular basis for the clear discrimination between non-cutaneous or dermal melanocytes and epidermal melanocytes, a difference that might be important in the pathogenesis of melanocyte-related diseases and melanomas.

Key words: Melanocytes, c-KIT, KITL, Endothelin, HGF, Mouse


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H. Aoki, Y. Yamada, A. Hara, and T. Kunisada
Two distinct types of mouse melanocyte: differential signaling requirement for the maintenance of non-cutaneous and dermal versus epidermal melanocytes
J. Cell Sci., August 1, 2009; 122(15): e1506 - e1506.
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