New Perspectives on Melanoma_ The Role of PAX3

These quiescent cells are characterised as being dct

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Unformatted text preview: ession continues as melanoblasts develop and migrate from the neural crest and persists in these cells in developing hair follicles [63]. Similar temporal expression is observed for Sox10, an early neural crest marker essential for the survival of undifferentiated neural crest cells [180]. Specification along the melanocyte lineage, first observed in neural crest cells overlaying and lateral to the neural tube at E10‐10.5, is denoted by the expression of melanoblast markers Mitf, Kit (Kit oncogene) and Dct (Dopachrome Tautomerase) [12,39‐43]. The melanoblasts expand a few hours later in the migration staging area from where they enter the dorsolateral pathway and migrate to the epidermis (E12.5‐E13.5) [44,45,63]. Once in the epidermis, melanoblasts are incorporated into developing hair follicles and begin to express Tyr (Tyrosinase) and TRP­1 (Tyrosine related protein­1) (E14.5) [43]. Melanogenesis marks the emergence of differentiated melanocytes (E16.5) [43]. Melanoblasts migrate to the epidermis and in humans differentiate into melanocytes which lie at the epidermal/dermal border [17,49‐51], whereas in mouse these die off [46‐48]. Melanocytes also populate the hair follicle matrix in both mouse and humans. These melanocytes show a molecular expression profile characteristic of maturing melanocytes, expressing Pax3, Sox10, Mitf, Kit, Dct, Tyr, TRP­1 and SILV [150]. 35 Chapter II – Medic and Ziman, 2009 Figure 2.2. Gene expression patterns in murine melanocytes during development. (A) represents temporal expression of the crucial genes during sequential stages of embryonic melanocyte development. (B) represents the hierarchy of melanocyte‐specific gene activation. Key factors in melanocyte development Pax3, also known as MSF (melanocyte specific factor) [73], is one of the earliest neural crest markers. It is expressed in neural crest precursors during neurulation, and later in the dorsal neural tube, dorsal root ganglion (DRG) and in cells entering the migration pathway in the dermomyotome [17]. Pax3 is crucial for neural cr...
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