Galanin Signaling in the Brain Regulates Color Pattern Formation in Zebrafish

Summary

Color patterns are prominent features of many animals and are of high evolutionary relevance. In basal vertebrates, color patterns are composed of specialized pigment cells that arrange in multilayered mosaics in the skin. Zebrafish ( Danio rerio), the preeminent model system for vertebrate color pattern formation, allows genetic screens as powerful approaches to identify novel functions in a complex biological system. Adult zebrafish display a series of blue and golden horizontal stripes, composed of black melanophores, silvery or blue iridophores, and yellow xanthophores. This stereotyped pattern is generated by self-organization involving direct cell contacts between all three types of pigment cells mediated by integral membrane proteins [ 1, 2, 3, 4, 5]. Here, we show that neuropeptide signaling impairs the striped pattern in a global manner. Mutations in the genes coding either for galanin receptor 1A ( npm/galr1A) or for its ligand galanin ( galn) result in fewer stripes, a pale appearance, and the mixing of cell types, thus resembling mutants with thyroid hypertrophy [ 6]. Zebrafish chimeras obtained by transplantations of npm/galr1A mutant blastula cells indicate that mutant pigment cells of all three types can contribute to a normal striped pattern in the appropriate host. However, loss of galr1A expression in a specific region of the brain is sufficient to cause the mutant phenotype in an otherwise wild-type fish. Increased thyroid hormone levels in mutant fish suggest that galanin signaling through Galr1A in the pituitary is an upstream regulator of the thyroid hormone pathway, which in turn promotes precise interactions of pigment cells during color pattern formation.

Graphical Abstract

Highlights

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  Zebrafish stripes are generated by three types of self-organizing pigment cells

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  Galanin signaling through Galr1A impairs zebrafish stripe formation globally

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  Galr1A function in a specific brain region is required for pigment cell interactions

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  Galanin signaling functions to downregulate thyroid hormone levels

Abstract

Eskova et al. show that the neuropeptide galanin functions in the zebrafish brain to regulate peripheral thyroid hormone levels. Mutations in either galanin or galr1A, one of its receptors, lead to elevated levels of T4 thyroid hormone resulting in an easily visible pigmentation phenotype due to impaired interactions between the pigment cells.