title: Zebrafish Leucocyte tyrosine kinase controls iridophore establishment, proliferation and survival.
abstract: The zebrafish striped pattern results from the interplay among three pigment cell types; black melanophores, yellow xanthophores and silvery iridophores, making it a valuable model to study pattern formation in vivo. It has been suggested that iridophore proliferation, dispersal and cell shape transitions play an important role during stripe formation; however, the underlying molecular mechanisms remain poorly understood. Using gain- and loss-of-function alleles of leucocyte tyrosine kinase (ltk) and a pharmacological inhibitor approach, we show that Ltk specifically regulates iridophore establishment, proliferation and survival. Mutants in shady/ltk lack iridophores and display an abnormal body stripe pattern. Moonstone mutants, ltk(mne) , display ectopic iridophores, suggesting hyperactivity of the mutant Ltk. The dominant ltk(mne) allele carries a missense mutation in a conserved position of the kinase domain that highly correlates with neuroblastomas in mammals. Chimeric analysis suggests a novel physiological role of Ltk in the regulation of iridophore proliferation by homotypic competition.
authors.affiliation: Max-Planck-Institut für Entwicklungsbiologie, Tübingen, Germany.
authors.forename: Andrey
authors.initials: A
authors.lastname: Fadeev
authors.affiliation: Max-Planck-Institut für Entwicklungsbiologie, Tübingen, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Krauss
authors.affiliation: Max-Planck-Institut für Entwicklungsbiologie, Tübingen, Germany.
authors.forename: Ajeet Pratap
authors.initials: AP
authors.lastname: Singh
authors.affiliation: Max-Planck-Institut für Entwicklungsbiologie, Tübingen, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Nüsslein-Volhard
mesh_terms: D000375:Aging; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001522:Behavior, Animal; D019521:Body Patterning; D002450:Cell Communication; D049109:Cell Proliferation; D002470:Cell Survival; D002856:Chromatophores / Q000166:cytology* / Q000201:enzymology*; D008547:Melanophores / Q000166:cytology / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D029961:Zebrafish Proteins; C000613254:Ltk protein, zebrafish; D011505:Protein-Tyrosine Kinases
keywords: homotypic competition; iridophores; leucocyte tyrosine kinase; pigment cells; tumorigenesis; zebrafish