Ctr1‐ing BRAF signaling with copper

Delta–Notch signal for survival. Finally, the authors demonstrate elegantly that stripe melanophores are in distant contact with xanthophores. They demonstrate by two distinct methods that long, fine processes project from melanophores toward xanthophores. These presumed intercellular connections provide a cellular mechanism for transmission of a survival signal directly from xanthophores to melanophores. In conclusion, Hamada et al. have shown that xanthophores are a distant (long range) source of Delta–Notch signal for melanophore survival, although the authors also speculate that involvement of the Delta–Notch signaling mediated by xanthophores is only a part of a complex mechanism for melanophore survival. Together with previous work, this study argues for the intriguing conclusion that the underlying basis for the Turing-type mechanism of zebrafish pigment pattern formation does not require physical diffusion of molecules, but instead results from direct cell–cell contacts mediating both shortand longrange signaling. Direct contact resulting in cell depolarization acts as a shortrange signal; Kir7.1 is likely involved in this. Similarly, long-range signaling is Delta–Notch dependent; long projections (cytonemes; Muller et al., 2013) of melanophores allow them to sense Delta expression in distant xanthophores. Further studies are desired to test whether Notch receptor proteins are localized at the tip of projection of melanophores and whether Delta ligand binding to Notch receptors occurs at the contact sites between melanophores and xanthophores. One final consideration concerns the recent discovery of a role in pigment pattern formation for the third pigment cell type in zebrafish, iridophores. Two recent studies have shown that three mutants, rose, shady, and transparent, lacking iridophores have altered pigment patterns on the skin of the trunk, strongly suggesting a role for this third pigment cell type in adult pigment pattern formation (Frohnhofer et al., 2013). However, it is noteworthy that whereas mutants such as panther, leopard, and jaguar perturb the stripe pattern in both of the trunk and fins, in the iridophoreless mutants, stripe formation is not affected in the anal and tail fins. Thus, stripe formation in both the trunk and the fins likely shares an underlying mechanism, but that in the trunk iridophores are additionally involved. Thus, further consideration needs to be given to how iridophores interact with melanophores and xanthophores if we are to fully understand how the zebrafish gets its stripes.