Abstract: | Melanocytes originate from the neural crest in vertebrates and migrate to the body surface where they differentiate into functional cells. Genes involved in melanocyte differentiation can be classified into two groups. One of them consists of the functional genes that control proteins specific to the function of the melanocyte. As the representative gene of this category, albino (c) locus in the mouse is considered to control tyrosinase, the key enzyme in melanogenesis. cDNA for mouse tyrosinase has been cloned and sequenced. The cDNA can be used to detect tyrosinase mRNA synthesized during melanocyte differentiation. On the other hand, genes such as brown (b) or pink-eyed dilution (p) have been assumed to control melanosome proteins. The other category consists of genes that regulate the expression of these functional genes directly or indirectly. In the mouse, so-called white-spotting genes and genes of the agouti series are considered to fall into this category. Based on the fact that mutations at the white-spotting loci result in the absence of melanocytes in a particular area of skin, it is assumed that some of these loci control the factors that promote either differentiation or migration of melanoblasts and are candidates for the classic regulator genes Genes at the agouti (a) locus in the mouse determine the type of melanin synthesized in hair follicle melanocytes, that is eumelanin or pheomelanin. An interesting feature of this locus is that the site of gene action is not within the melanocytes but in the cells surrounding them. The results of our study indicate that the gene product of the a-locus interacts with α-MSH at the α-MSH receptor site, regulates the cellular cAMP level via a signal transduction system and, in turn, determines the type of melanin synthesized in the cells. |