Although melanocytes represent one of several terminally differentiated neural crest-derived lineages, they exhibit a surprisingly high degree of phenotypic plasticity (Adameyko et al., 2009, Real et al., 2006). Interestingly, the cell fate switching in melanocytes can be observed in vivo under pathologic conditions including nevi, as nevus cells phenotypically resemble Schwann cells in multiple ways (Aso et al., 1988). However, it is unclear whether the phenotypic switch occurs coincidental with nevus formation or whether it functionally contributes to the tumor suppressive effect of nevigenesis.

BRAFV600E is the most prevalent mutation in melanoma (Girotti et al., 2014). Our laboratory generated a transgenic mouse in which BRAFV600E is expressed in melanocytes (Goel et al., 2009). The BRAFV600E mice exhibited skin hyperpigmentation, melanocytic hyperplasia and developed melanomas at a low frequency; moreover, metastatic melanomas can be induced in combination with Cdkn2a+/-, Tp53+/-, Arf-/-or UV irradiation (Luo et al., 2013).