New Perspectives on Melanoma_ The Role of PAX3

Pten regulates progression through the g1 cell cycle

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Unformatted text preview: melanoblast and melanocyte stem cells in a process which is dependent upon Wnt signalling [19,111]. The prerequisite for maintenance of quiescent melanocyte stem cells is downregulation of the Wnt‐dependant differentiation program. Indeed, the bulge area is described as a Wnt “protected” area with increased expression of Wnt inhibitors such as Sfrp1, Dab2 and Dkk3 in bulge cells [118,192]. These inhibitors decrease Wnt signalling as well as Mitf levels [111], and as a result induce cell cycle exit [193] and melanocyte stem cell quiescence. 38 Chapter II – Medic and Ziman, 2009 Multifunctional role of Pax3 during melanocyte development and maturation Studies of temporal gene patterning of melanocytes in the developing embryo indicate that although Pax3 is one of the first genes in the melanocyte specification hierarchy, it clearly plays a much broader, multifunctional role during normal melanocyte development (Figure 2.3). Here, we review the involvement of Pax3 in differentiation, survival and migration of melanocytes. By analysis of Pax3 function in normal melanocyte development we seek to gain not only a better understanding of its involvement in adult differentiated melanocytes, but also a greater appreciation of its role in melanoma, where it is commonly expressed. Figure 2.3. Multiple roles of Pax3 in melanocyte development and maturation. Schematic representation of the cooperation between Pax3 and other factors involved in regulating “stemness”, differentiation, survival and migration. 39 Chapter II – Medic and Ziman, 2009 Pax3 and maintenance of the undifferentiated state One of the best described roles for Pax3 is regulation of melanocyte differentiation; as recently suggested it acts as a “switch” or a “nodal point” in differentiation of these cells [19]. Pax3 is thought to activate melanocyte lineage specification but at the same time it acts to block terminal differentiation, thus acting to maintain a pool of undifferentiated melanoblast cells. A role...
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This document was uploaded on 03/06/2014 for the course CHEMISTRY 12 at National University of Singapore.

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