New Perspectives on Melanoma_ The Role of PAX3

Melanogenesis takes place in the specialised

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Unformatted text preview: aneous formation of the new hair that grows upwards, finally protruding through the epidermis. Bulge melanocyte stem cells are activated at early anagen to divide and generate a population of cells that remain in the bulge as stem cells as well as amplifying progeny that extend towards follicular papilla [78]. These two populations become segregated in the growing follicle and amplifying progeny localise to the hair matrix, proliferate and mature into fully differentiated melanocytes which produce melanin, transfer it to the hair keratinocytes and then die by apoptosis during catagen [83]. 10 Chapter I – Thesis Overview Figure 1.1.5. Schematic representation of the hair cycle. The figure shows successive stages of the hair cycle: anagen, catagen and telogen. Sg is sebaceous glad, Ap is arrector pilli muscle, Bg is bulge, Dp is dermal papilla, Hs is hair shaft, IRS is inner root sheath, ORS is outer root sheath, CTS is connective tissue sheath (adapted from [84]). 1.3. Melanocyte function: Regulation of melanogenesis The main function of melanocytes is pigment production (or melanogenesis), providing photoprotection and thermoregulation, thus contributing to the skin’s protective function as the body’s main barrier to the external environment. During melanogenesis, the precursor tyrosine is initially converted into dopaquinone, from which biosynthesis proceeds, via independent mechanisms, to produce two forms of melanin pigment, pheomelanin and eumelanin (Figure 1.1.6.). Production of pheomelanin is spontaneously initiated in the presence of cysteine, whereas eumelanin synthesis (in the absence of cysteine) involves action of three main 11 Chapter I – Thesis Overview melanocytic enzymes: tyrosinase (TYR), tyrosinase‐related protein‐1 (TYRP1) and dopachrome tautomerase (DCT/TYRP2) [85,86]. Figure 1.1.6. Biochemistry of melanogenesis. When tyrosine is oxidized by tyrosinase, dopaquinone is produced as the immediate product. From dopaquinone two different reactions are possible, formation of eu‐ or pheomelanin. A) I...
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