Zebrafish Leucocyte tyrosine kinase controls iridophore establishment, proliferation and survival

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.