Abstract：
The canonical Wnt/β-catenin pathway governs a multitude of developmental processes in various cell lineages, including the melanocyte lineage. Indeed, β-catenin regulates Mitf-M transcription, the master regulator of this lineage. The first wave of melanocytes to colonize the skin is directly derived from neural crest cells, while the second wave of melanocytes is derived from Schwann-cell precursors (SCPs). We investigated the influence of β-catenin in the development of melanocytes of the first and second waves by generating mice expressing a constitutively active form of β-catenin in cells expressing tyrosinase. Constitutive activation of β-catenin did not affect the development of truncal melanoblasts but led to marked hyperpigmentation of the paws. By activating β-catenin at various stages of development (E8.5-E11.5), we showed that the activation of β-catenin in bipotent SCPs favored melanoblast specification at the expense of Schwann cells in the limbs within a specific temporal window. Furthermore, in vitro hyperactivation of the Wnt/β-catenin pathway, which is required for melanocyte development, induces activation of Mitf-M, in turn repressing FoxD3 expression. In conclusion, β-catenin overexpression promotes SCP cell fate decisions towards the melanocyte lineage.
摘要：
典型的Wnt/β-catenin途径控制着各种细胞谱系中的多种发育过程。包括黑素细胞谱系.的确,β-连环蛋白调节Mitf-M转录，这个血统的主要监管者。第一波定居在皮肤上的黑素细胞直接来自神经c细胞，而第二波黑素细胞来自雪旺氏细胞前体（SCP）。我们通过在表达酪氨酸酶的细胞中产生表达组成型活性形式的β-catenin的小鼠，研究了β-catenin在第一和第二波黑素细胞发育中的影响。β-catenin的本构激活不会影响躯干成黑素细胞的发育，但会导致爪子的明显色素沉着。通过在不同的发育阶段激活β-连环蛋白（E8.5-E11.5），我们表明，双能SCP中β-catenin的激活有利于黑素细胞的特化，而在特定的时间窗口内损害了四肢中的雪旺氏细胞。此外，Wnt/β-catenin通路的体外超激活，这是黑素细胞发育所必需的，诱导Mitf-M的激活，反过来抑制FoxD3表达。总之,β-连环蛋白过表达促进SCP细胞命运决定向黑素细胞谱系。
