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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
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Disease relevance of Melanocytes


Psychiatry related information on Melanocytes

  • We also conclude that the critical period of SLF dependence lasts about 4 days, ending about the time that melanocytes differentiate, as indicated by the presence of functional melanosomes, but before their overt melanization [6].

High impact information on Melanocytes

  • To identify Mitf-dependent Kit transcriptional targets in primary melanocytes, microarray studies were undertaken [7].
  • Kit/SCF signaling and Mitf-dependent transcription are both essential for melanocyte development and pigmentation [7].
  • Subsets of HSCR individuals also present with neural crest-derived melanocyte deficiencies (Hirschsprung-Waardenburg, HSCR-WS, MIM #277580) [8].
  • In mammals the relative proportions of phaeomelanin and eumelanin are regulated by melanocyte stimulating hormone (MSH), which acts via its receptor (MC1R), on melanocytes, to increase the synthesis of eumelanin and the product of the agouti locus which antagonises this action [9].
  • Interaction of endothelin-3 with endothelin-B receptor is essential for development of epidermal melanocytes and enteric neurons [10].

Chemical compound and disease context of Melanocytes


Biological context of Melanocytes


Anatomical context of Melanocytes

  • Our studies show that mouse Gl protein function is absolutely required for osteoclast and melanocyte maturation and function [21].
  • Second, we conclude that keratinocyte expression of membrane-bound SCF results in the postnatal maintenance of epidermal melanocytes in mice [22].
  • Analysis of the response in successfully treated mice revealed elevated levels of CD8(+) T cells specific for a nonameric peptide consisting of residues 180-188 of the melanocyte differentiation antigen tyrosinase-related protein (TRP)2 [23].
  • We analyzed the effects of recombinant human SCF (r-hSCF, 5-50 micrograms/kg/day, injected subcutaneously) on mast cells and melanocytes in a phase I study of 10 patients with advanced breast carcinoma [4].
  • Knockdown of endogenous Slp2-a protein by small-interfering RNAs (siRNAs) markedly reduced the number of melanosomes in the cell periphery of mouse melanocytes ('peripheral dilution') [24].

Associations of Melanocytes with chemical compounds


Gene context of Melanocytes

  • Our findings indicate that MITF is critically involved in melanocyte differentiation [2].
  • Sox10 also has functions not mediated by ErbB3, for instance in the melanocyte lineage [30].
  • Cutaneous effects of most Dsk mutations are limited to melanocytes, except for the Keratin 2e and Egfr mutations, in which hyperkeratosis and epidermal thickening precede epidermal melanocytosis by 3-6 wk [31].
  • Absence of endogenous TRP-2-INT2 expression in melanocytes was also confirmed by lack of recognition of HLA-A*68011-transduced, TRP-2(+) melanocyte lines by CTL 128 [32].
  • By gel shift analysis, we show that in mitogen-dependent normal melanocytes, external growth factors tightly controlled the levels of growth-promoting free E2F DNA binding activity, composed largely of E2F2 and E2F4, and the growth-suppressive E2F4-p130 complexes [33].

Analytical, diagnostic and therapeutic context of Melanocytes


  1. Mutations in the gene encoding B, a novel transporter protein, reduce melanin content in medaka. Fukamachi, S., Shimada, A., Shima, A. Nat. Genet. (2001) [Pubmed]
  2. Ectopic expression of MITF, a gene for Waardenburg syndrome type 2, converts fibroblasts to cells with melanocyte characteristics. Tachibana, M., Takeda, K., Nobukuni, Y., Urabe, K., Long, J.E., Meyers, K.A., Aaronson, S.A., Miki, T. Nat. Genet. (1996) [Pubmed]
  3. Nr-CAM is a target gene of the beta-catenin/LEF-1 pathway in melanoma and colon cancer and its expression enhances motility and confers tumorigenesis. Conacci-Sorrell, M.E., Ben-Yedidia, T., Shtutman, M., Feinstein, E., Einat, P., Ben-Ze'ev, A. Genes Dev. (2002) [Pubmed]
  4. Recombinant human stem cell factor (kit ligand) promotes human mast cell and melanocyte hyperplasia and functional activation in vivo. Costa, J.J., Demetri, G.D., Harrist, T.J., Dvorak, A.M., Hayes, D.F., Merica, E.A., Menchaca, D.M., Gringeri, A.J., Schwartz, L.B., Galli, S.J. J. Exp. Med. (1996) [Pubmed]
  5. Differentiation and tumorigenicity of human malignant melanocytes in relation to their culture conditions. Aubert, C., Rougé, F., Galindo, J.R. J. Natl. Cancer Inst. (1984) [Pubmed]
  6. Transient steel factor dependence by neural crest-derived melanocyte precursors. Morrison-Graham, K., Weston, J.A. Dev. Biol. (1993) [Pubmed]
  7. Bcl2 regulation by the melanocyte master regulator Mitf modulates lineage survival and melanoma cell viability. McGill, G.G., Horstmann, M., Widlund, H.R., Du, J., Motyckova, G., Nishimura, E.K., Lin, Y.L., Ramaswamy, S., Avery, W., Ding, H.F., Jordan, S.A., Jackson, I.J., Korsmeyer, S.J., Golub, T.R., Fisher, D.E. Cell (2002) [Pubmed]
  8. Sox10 mutation disrupts neural crest development in Dom Hirschsprung mouse model. Southard-Smith, E.M., Kos, L., Pavan, W.J. Nat. Genet. (1998) [Pubmed]
  9. Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans. Valverde, P., Healy, E., Jackson, I., Rees, J.L., Thody, A.J. Nat. Genet. (1995) [Pubmed]
  10. Interaction of endothelin-3 with endothelin-B receptor is essential for development of epidermal melanocytes and enteric neurons. Baynash, A.G., Hosoda, K., Giaid, A., Richardson, J.A., Emoto, N., Hammer, R.E., Yanagisawa, M. Cell (1994) [Pubmed]
  11. Cell surface antigens of human melanocytes and melanoma. Expression of adenosine deaminase binding protein is extinguished with melanocyte transformation. Houghton, A.N., Albino, A.P., Cordon-Cardo, C., Davis, L.J., Eisinger, M. J. Exp. Med. (1988) [Pubmed]
  12. Effect of azelaic acid on human malignant melanoma. Nazzaro-Porro, M., Passi, S., Zina, G., Bernengo, A., Breathnach, A., Gallagher, S., Morpurgo, G. Lancet (1980) [Pubmed]
  13. Different cis-acting elements are involved in the regulation of TRP1 and TRP2 promoter activities by cyclic AMP: pivotal role of M boxes (GTCATGTGCT) and of microphthalmia. Bertolotto, C., Buscà, R., Abbe, P., Bille, K., Aberdam, E., Ortonne, J.P., Ballotti, R. Mol. Cell. Biol. (1998) [Pubmed]
  14. Clinical significance of alpha(v)beta3 integrin and intercellular adhesion molecule-1 expression in cutaneous malignant melanoma lesions. Natali, P.G., Hamby, C.V., Felding-Habermann, B., Liang, B., Nicotra, M.R., Di Filippo, F., Giannarelli, D., Temponi, M., Ferrone, S. Cancer Res. (1997) [Pubmed]
  15. Effect of 17 beta-estradiol on the growth of estrogen receptor-positive human melanoma in vitro and in athymic mice. Feucht, K.A., Walker, M.J., Das Gupta, T.K., Beattie, C.W. Cancer Res. (1988) [Pubmed]
  16. The cleavage of microphthalmia-associated transcription factor, MITF, by caspases plays an essential role in melanocyte and melanoma cell apoptosis. Larribere, L., Hilmi, C., Khaled, M., Gaggioli, C., Bille, K., Auberger, P., Ortonne, J.P., Ballotti, R., Bertolotto, C. Genes Dev. (2005) [Pubmed]
  17. c-Kit triggers dual phosphorylations, which couple activation and degradation of the essential melanocyte factor Mi. Wu, M., Hemesath, T.J., Takemoto, C.M., Horstmann, M.A., Wells, A.G., Price, E.R., Fisher, D.Z., Fisher, D.E. Genes Dev. (2000) [Pubmed]
  18. A role for dipeptidyl peptidase IV in suppressing the malignant phenotype of melanocytic cells. Wesley, U.V., Albino, A.P., Tiwari, S., Houghton, A.N. J. Exp. Med. (1999) [Pubmed]
  19. Genetic and biochemical evidence that haploinsufficiency of the Nf1 tumor suppressor gene modulates melanocyte and mast cell fates in vivo. Ingram, D.A., Yang, F.C., Travers, J.B., Wenning, M.J., Hiatt, K., New, S., Hood, A., Shannon, K., Williams, D.A., Clapp, D.W. J. Exp. Med. (2000) [Pubmed]
  20. Self-tolerance to the murine homologue of a tyrosinase-derived melanoma antigen: implications for tumor immunotherapy. Colella, T.A., Bullock, T.N., Russell, L.B., Mullins, D.W., Overwijk, W.W., Luckey, C.J., Pierce, R.A., Restifo, N.P., Engelhard, V.H. J. Exp. Med. (2000) [Pubmed]
  21. Grey-lethal mutation induces severe malignant autosomal recessive osteopetrosis in mouse and human. Chalhoub, N., Benachenhou, N., Rajapurohitam, V., Pata, M., Ferron, M., Frattini, A., Villa, A., Vacher, J. Nat. Med. (2003) [Pubmed]
  22. Murine cutaneous mastocytosis and epidermal melanocytosis induced by keratinocyte expression of transgenic stem cell factor. Kunisada, T., Lu, S.Z., Yoshida, H., Nishikawa, S., Nishikawa, S., Mizoguchi, M., Hayashi, S., Tyrrell, L., Williams, D.A., Wang, X., Longley, B.J. J. Exp. Med. (1998) [Pubmed]
  23. Elucidating the autoimmune and antitumor effector mechanisms of a treatment based on cytotoxic T lymphocyte antigen-4 blockade in combination with a B16 melanoma vaccine: comparison of prophylaxis and therapy. van Elsas, A., Sutmuller, R.P., Hurwitz, A.A., Ziskin, J., Villasenor, J., Medema, J.P., Overwijk, W.W., Restifo, N.P., Melief, C.J., Offringa, R., Allison, J.P. J. Exp. Med. (2001) [Pubmed]
  24. Rab27A-binding protein Slp2-a is required for peripheral melanosome distribution and elongated cell shape in melanocytes. Kuroda, T.S., Fukuda, M. Nat. Cell Biol. (2004) [Pubmed]
  25. Action of the e locus of mice in the response of phaeomelanic hair follicles to alpha-melanocyte-stimulating hormone in vitro. Tamate, H.B., Takeuchi, T. Science (1984) [Pubmed]
  26. Melanocyte lineage-specific antigen gp100 is recognized by melanoma-derived tumor-infiltrating lymphocytes. Bakker, A.B., Schreurs, M.W., de Boer, A.J., Kawakami, Y., Rosenberg, S.A., Adema, G.J., Figdor, C.G. J. Exp. Med. (1994) [Pubmed]
  27. Endocrine responsiveness in human melanocytes and melanoma cells in culture. Fuller, B.B., Meyskens, F.L. J. Natl. Cancer Inst. (1981) [Pubmed]
  28. Mitotic activity in non-neoplastic melanocytes in vivo as determined by histochemical, autoradiographic, and electron microscope studies. Jimbow, K., Roth, S.I., Fitzpatrick, T.B., Szabo, G. J. Cell Biol. (1975) [Pubmed]
  29. Identification of a melanosomal matrix protein encoded by the murine si (silver) locus using "organelle scanning". Zhou, B.K., Kobayashi, T., Donatien, P.D., Bennett, D.C., Hearing, V.J., Orlow, S.J. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  30. The transcription factor Sox10 is a key regulator of peripheral glial development. Britsch, S., Goerich, D.E., Riethmacher, D., Peirano, R.I., Rossner, M., Nave, K.A., Birchmeier, C., Wegner, M. Genes Dev. (2001) [Pubmed]
  31. Genetics of dark skin in mice. Fitch, K.R., McGowan, K.A., van Raamsdonk, C.D., Fuchs, H., Lee, D., Puech, A., Hérault, Y., Threadgill, D.W., Hrabé de Angelis, M., Barsh, G.S. Genes Dev. (2003) [Pubmed]
  32. Translation of a retained intron in tyrosinase-related protein (TRP) 2 mRNA generates a new cytotoxic T lymphocyte (CTL)-defined and shared human melanoma antigen not expressed in normal cells of the melanocytic lineage. Lupetti, R., Pisarra, P., Verrecchia, A., Farina, C., Nicolini, G., Anichini, A., Bordignon, C., Sensi, M., Parmiani, G., Traversari, C. J. Exp. Med. (1998) [Pubmed]
  33. Deregulated E2F transcriptional activity in autonomously growing melanoma cells. Halaban, R., Cheng, E., Smicun, Y., Germino, J. J. Exp. Med. (2000) [Pubmed]
  34. Intermediate filaments in malignant melanomas. Identification and use as marker in surgical pathology. Ramaekers, F.C., Puts, J.J., Moesker, O., Kant, A., Vooijs, G.P., Jap, P.H. J. Clin. Invest. (1983) [Pubmed]
  35. Altered proopiomelanocortin gene expression in adrenocorticotropin-producing nonpituitary tumors. Comparative studies with corticotropic adenomas and normal pituitaries. de Keyzer, Y., Bertagna, X., Lenne, F., Girard, F., Luton, J.P., Kahn, A. J. Clin. Invest. (1985) [Pubmed]
  36. Detection of melanoma cells in peripheral blood by means of reverse transcriptase and polymerase chain reaction. Smith, B., Selby, P., Southgate, J., Pittman, K., Bradley, C., Blair, G.E. Lancet (1991) [Pubmed]
  37. Expression of the neuroectodermal intermediate filament nestin in human melanomas. Flørenes, V.A., Holm, R., Myklebost, O., Lendahl, U., Fodstad, O. Cancer Res. (1994) [Pubmed]
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