Galanin Signaling in the Brain Regulates Color Pattern Formation in Zebrafish
Anastasia Eskova, Hans Georg Frohnhöfer, Christiane Nüsslein‐Volhard, Uwe Irion
Abstract
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 [1Frohnhöfer H.G. Krauss J. Maischein H.M. Nüsslein-Volhard C. Iridophores and their interactions with other chromatophores are required for stripe formation in zebrafish.Development. 2013; 140: 2997-3007Crossref PubMed Scopus (122) Google Scholar, 2Iwashita M. Watanabe M. Ishii M. Chen T. Johnson S.L. Kurachi Y. Okada N. Kondo S. Pigment pattern in jaguar/obelix zebrafish is caused by a Kir7.1 mutation: implications for the regulation of melanosome movement.PLoS Genet. 2006; 2: e197Crossref PubMed Scopus (103) Google Scholar, 3Maderspacher F. Nüsslein-Volhard C. Formation of the adult pigment pattern in zebrafish requires leopard and obelix dependent cell interactions.Development. 2003; 130: 3447-3457Crossref PubMed Scopus (113) Google Scholar, 4Singh A.P. Nüsslein-Volhard C. Zebrafish stripes as a model for vertebrate colour pattern formation.Curr. Biol. 2015; 25: R81-R92Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar, 5Watanabe M. Iwashita M. Ishii M. Kurachi Y. Kawakami A. Kondo S. Okada N. Spot pattern of leopard Danio is caused by mutation in the zebrafish connexin41.8 gene.EMBO Rep. 2006; 7: 893-897Crossref PubMed Scopus (142) Google Scholar]. 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 [6McMenamin S.K. Bain E.J. McCann A.E. Patterson L.B. Eom D.S. Waller Z.P. Hamill J.C. Kuhlman J.A. Eisen J.S. Parichy D.M. Thyroid hormone-dependent adult pigment cell lineage and pattern in zebrafish.Science. 2014; 345: 1358-1361Crossref PubMed Scopus (117) Google Scholar]. 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.