nacre encodes a zebrafish microphthalmia-related protein that regulates neural-crest-derived pigment cell fate

nacre harbors an inactivating mutation of the mitfa gene, rendering the fish devoid of pigmented melanocytes.

“For example, the zebrafish nacre (nac) mutant harbors an an inactivating mutation in the mitfa gene and are devoid of nearly all embryonic and adult melanophores (Lister et al., 1999), emphasizing the key role of this transcription factor as a master regulator of this cell type.”

Common strategies to reduce zebrafish skin pigmentation can be grouped into two categories: chemical compounds interfering with melanin synthesis, most popularly PTU, and pigmentation mutants.

“Common strategies to reduce zebrafish skin pigmentation can be grouped in two categories: 1) use of chemical compounds interfering with the synthesis of melanin, the most popular one being 1-phenyl-2-thiourea (PTU)8; 2) use of pigmentation mutants in which genes controlling either pigment formation, chromatophore formation or interactions between chromatophores have been inactivated469.”

The nacre mutation does not affect the population of cells forming the retinal pigment epithelium, so this structure is still pigmented in the nacre single mutant.

“Since the nacre mutation does not affect the population of cells forming the RPE, this structure is still pigmented in this single mutant.”

The nacre mutant lacks all melanophores due to a mutation in the mitfa gene.

“The nacrew2/w2 mutant lacks all melanophores due to a mutation in the mitfa gene9.”

The combinatorial crystal mutant (albb4/b4;nacrew2/w2;roya9/a9) was generated by sequentially crossbreeding three single mutant strains: nacrew2/w2, roya9/a9 and albb4/b4.

“The combinatorial crystal mutant (albb4/b4;nacrew2/w2;roya9/a9) was generated by sequentially crossbreeding three different single mutant strains, namely nacrew2/w2 (ref. 9), roya9/a9 (ref. 4) and albb4/b4 (ref. 18) mutants.”

Mitfa is necessary and sufficient to upregulate numerous melanocyte differentiation genes, including those controlling melanin synthesis.

“Like its mammalian counterpart, MITF, Mitfa has been proven necessary and sufficient to upregulate numerous melanocyte differentiation genes, including those controlling melanin synthesis (e.g. dct, silva and tyrosinase).”

Mitfa is the master regulator of melanocyte fate.

“Mitfa is thus dubbed the ‘master regulator’ of melanocyte fate choice [13, 21, 25].”

At approximately 22 hpf, ltk and mitfa are upregulated in the tfec+; foxd3- premigratory cells of the trunk, indicating they correspond to partially restricted progenitors capable of generating pigment cells.

“At approximately 22 hpf, ltk and mitfa are upregulated in the tfec+; foxd3- premigratory cells of the trunk [11, 14, 21], indicating that they correspond to partially restricted progenitors, capable of generating pigment cells”

Mutants for mitfa, which lack melanophores, have the dense morphology iridophores over a broader area than wild-type fish.

“Prior work has hinted at this possibility as mutants for melanophore-inducing transcription factor (mitfa), which lack melanophores, have the dense morphology iridophores (characteristic of interstripe zones) over a broader area than wild-type fish14,27.”

In mitfaw2 mutants, melanophores are missing owing to a defect in their specification; in albino mutants, melanophores are present but lack melanin.

“In mitfaw2 mutants, melanophores are missing owing to a defect in their specification; in albino mutants, melanophores are present but lack melanin27,36”

The nacre mutant has a complete lack of melanocytes due to a mutation in the gene encoding mitfa.

“The nacre mutant (Figure 1B) has a complete lack of melanocytes due to a mutation in the gene encoding the mitfa gene.”

The increase in iridophores in mitfa mutants reveals a shared bipotent progenitor, the melanoiridoblast.

“interpreted as revealing a shared bipotent progenitor, a melanoiridoblast [15], [19].”

mitfa mutants show an increase in iridophores accompanying the absence of melanocytes.

“mitfa mutants show an intriguing increase in iridophores accompanying the absence of melanocytes”

mitfa and ltk are activated widely by 22 hpf, with pnp4a following soon after.

“However, mitfa and ltk are activated widely by 22 hpf [9], [19], with pnp4a following soon after [15].”