MC1R, EDNRB and kit signaling in pigmentation regulation related disorders Book Chapter

Pino, J, Kos, L. (2013). MC1R, EDNRB and kit signaling in pigmentation regulation related disorders . 57-88.

cited authors

  • Pino, J; Kos, L



  • Skin and hair pigmentation results from the presence and distribution of melanin in keratinocytes. Melanin is produced by melanocytes in well-defined chemical reactions where tyrosinase is the rate-limiting enzyme, and then transferred to keratinocytes in small vesicles called melanosomes. Melanocytes are derived from the neural crest, a transient embryonic population of cells that emanate from the forming central nervous system. During development the proliferation, survival, migration and differentiation of melanocyte precursors are regulated by a series of molecules secreted in the local environment that trigger the activation of intracellular signaling cascades. Once melanocytes reach their final destination in the skin and hair follicles, a combination of these and other signaling molecules produced by the neighboring keratinocytes, fibroblasts and vascular endothelial cells regulate their physiological functions including melanin production. Genetic variants or mutations in the genes that code for the various components of these signaling pathways lead to pigmentary disorders and increased risk for melanoma. Here we will review three of the major signaling pathways involved in the establishment of mammalian skin and hair coloration via the regulation of tyrosinase activity. The Melanocortin 1 Receptor pathway acts in differentiated melanocytes regulating the type of melanin produced. Particular variants in this gene are responsible for fair skin and red hair traits, which have been associated with high risk for skin cancer. The Endothelin Receptor B and KIT signaling pathways play essential roles during melanocyte development and when mutated lead to the hypopigmentation phenotypes in Waardenburg-Shah syndrome and piebaldism, respectively. We will discuss how these three pathways may interact at the cellular level to produce the final pigmentation patterns observed in mice and humans. © 2013 Nova Science Publishers, Inc.

publication date

  • December 1, 2013

International Standard Book Number (ISBN) 13

start page

  • 57

end page

  • 88