Involvement of Delta/Notch signaling in zebrafish adult pigment stripe patterning

Abstract

The skin pigment pattern of zebrafish is a good model system in which to study the mechanism of biological pattern formation. Although it is known that interactions between melanophores and xanthophores play a key role in the formation of adult pigment stripes, molecular mechanisms for these interactions remain largely unknown. Here, we show that Delta/Notch signaling contributes to these interactions. Ablation of xanthophores in yellow stripes induced the death of melanophores in black stripes, suggesting that melanophores require a survival signal from distant xanthophores. We found that deltaC and notch1a were expressed by xanthophores and melanophores, respectively. Moreover, inhibition of Delta/Notch signaling killed melanophores, whereas activation of Delta/Notch signaling ectopically in melanophores rescued the survival of these cells, both in the context of pharmacological inhibition of Delta/Notch signaling and after ablation of xanthophores. Finally, we showed by in vivo imaging of cell membranes that melanophores extend long projections towards xanthophores in the yellow stripes. These data suggest that Delta/Notch signaling is responsible for a survival signal provided by xanthophores to melanophores. As cellular projections can enable long-range interaction between membrane-bound ligands and their receptors, we propose that such projections, combined with direct cell-cell contacts, can substitute for the effect of a diffusible factor that would be expected by the conventional reaction-diffusion (Turing) model.

Mathematically guided approaches to distinguish models of periodic patterning

“…Contact-dependent depolarization of membrane potential controls repulsion between melanophores and xanthophores (Inaba et al, 2012;Iwashita et al, 2006). Meanwhile, melanophores receive Notch-dependent survival signals by extending long cell protrusions to distant xanthophores (Hamada et al, 2014), controlling melanophore stripe width.…”

Modelling stripe formation in zebrafish: an agent-based approach

“…Three main kinds of pigment cells make up the striped pattern on zebrafish: black melanophores, yellow xanthophores and silvery iridophores [4][5][6][7][8]. Iridophores give the pattern its shiny appearance and appear all over the skin, though in different forms in black stripes and yellow interstripes [4,5,9].…”

“…Numerous experimental studies have been conducted to elucidate the cellular interactions that drive pattern formation. These experiments range from using laser or transgenic ablation to remove pigment cells in vivo [5,7,12,16,17] to observing pairs of cells interacting in vitro [18,19] and exploring altered cell behaviour through mutational analysis, transplantation and other methods [14,20,21]. Researchers also study time-lapse images of wild-type development [10,15,16,20,22] and analyse mutations [4,8,10,11,[14][15][16][19][20][21][22][23][24][25].…”

The Physiological Characterization of Connexin41.8 and Connexin39.4, Which Are Involved in the Striped Pattern Formation of Zebrafish

“…The membrane resting potential formed by Kir7.1, the inward rectifier potassium channel 7.1, is important for establishing clear boundaries between melanophores and xanthophores, and this channel functions as a short range factor in the Turing model (22,29,30). Notch-Delta signaling from xanthophores (Delta) to melanophores (Notch) is required for melanophore survival and acts as a long range factor in this model (22,31). The zebrafish has a third type of pigment cell, the iridophore, which has reflecting internal structures and is involved in skin pattern formation by providing the initial conditions of the pattern formation system (32).…”