Another study in which mouse NC cultures were treated with Edn3, Edn1, or Kitl showed an increase in the number of melanocyte progenitors; however, Kitl alone was not sufficient to induce the differentiation of melanocyte progenitors into mature melanocytes. Mature melanocytes were however observed, when treatment with Kitl was followed by Edn3 or Edn1 (Reid et al., 1996). As previously noted, although in the absence of Edn3, Kit-positive and DOPA-positive cells arose in mouse NC cultures, Ednrb signaling was required for the generation of fully pigmented melanocytes (Ono et al., 1998). These findings hint to a specific requirement for Ednrb signaling, independent of Kit signaling, in melanocyte differentiation. This requirement for Ednrb in the final phase of melanocyte differentiation may occur cell-autonomously, as suggested by the inability of Ednrb null cells to generate pigment even in the presence of Kitl (Hou et al., 2004). Together these findings point at a cooperative interaction between Kit and Ednrb signaling in melanocyte development, with Ednrb signaling being specifically required in the final differentiation step
This paragraph discusses how Ednrb is needed in order to further a melanocyte into melanoma, even if Kitl (another signaling pathway) is present. Therefore, this is the direct link to melanoma.
(NB)