Differential contribution of direct-developing and stem cell-derived melanocytes to the zebrafish larval pigment pattern

Abstract

The extent of adult stem cell involvement in embryonic growth is often unclear, as reliable markers or assays for whether a cell is derived from an adult stem cell, such as the Melanocyte Stem Cell (MSC), are typically not available. We have previously shown that two lineages of melanocytes can contribute to the larval zebrafish pigment pattern. The embryo first develops an ontogenetic pattern that is largely composed of ErbB-independent, direct-developing melanocytes. This population can be replaced during regeneration by an ErbB-dependent MSC-derived population following melanocyte ablation. In this study, we developed a melanocyte differentiation assay, used together with drugs that ablate the MSC, to investigate whether MSC-derived melanocytes contribute to the ontogenetic pattern. We found that essentially all melanocytes that develop before 3 dpf arise from the ErbB-independent, direct-developing population. Similarly, late-developing (after 3 dpf) melanocytes of the head are also ErbB independent. In contrast, the melanocytes that develop after three days postfertilization in the lateral and dorsal stripe are sensitive to ErbB inhibitor, indicating that they are derived from the MSC. We show that melanocyte regeneration mutants kitj1e99 and skiv2l2j24e1, that are grossly normal for the overall ontogenetic pattern, also lack the MSC-derived contribution to the lateral stripe. This result suggests that the underlying regeneration defect of these mutations is a defect in MSC regulation. We suggest that the regulative functions of the MSC may serve quality control roles during larval development, in addition to its established roles in larval regeneration and growth and homeostasis in the adult.

Combined zebrafish-yeast chemical-genetic screens reveal gene–copper-nutrition interactions that modulate melanocyte pigmentation

“…3F). The timing of action of U0126 on melanocyte pigmentation is consistent with the known kinetics of appearance of the rate-limiting copper-dependent enzyme tyrosinase in development (Hultman and Johnson, 2010). We compared the genome-wide chemical-genetic profiles of U0126, CI-1040 and neocuproine to determine the potential target pathways of U0126.…”

On the embryonic origin of adult melanophores: the role of ErbB and Kit signalling in establishing melanophore stem cells in zebrafish

“…Morpholino and small molecule inhibitor studies show that both regenerating and adult melanophores require ErbB3b signalling during the first day of embryogenesis when NC cells delaminate and migrate (Budi et al, 2008;Hultman et al, 2009;Johnson et al, 2011;Budi et al, 2011). These findings support a model in which ErbB signalling is required in the early embryo to establish both the peripheral nervous system and the melanophore stem cells that later generate the adult melanophore pattern (Hultman et al, 2009;Hultman and Johnson, 2010).…”

“…In adult erbb3b (also known as hypersensitive, hps and picasso) mutants, melanophores are drastically reduced but the larval melanophore pattern appears normal (Whitfield et al, 1996;Budi et al, 2008;Hultman et al, 2009;Hultman and Johnson, 2010). Mutations in erbb3b as well as in erbb2 (kitzelig, kiz) not only cause defects in pigmentation, but also in the peripheral nervous system and lateral line glia (Lyons et al, 2005;Rojas-Muñoz et al, 2009).…”

Involvement of the mitfa gene in the development of pigment cell in Japanese ornamental (Koi) carp (Cyprinus carpio L.)

“…Pigment cells are derived from the embryonic neural crest (Hultman and Johnson, 2010). Skin pigmentation is a complex process involving a series of cellular, genetic, and physiological factors (Colihueque, 2010).…”