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.

Ontogenetic and phylogenetic simplification during white stripe evolution in clownfishes

“…To determine if leucophores or iridophores are involved in white stripe formation in A . ocellaris , we tested whether the drug TAE684 (TAE), known as an inhibitor of leukocyte tyrosine kinase (Ltk) and anaplastic lymphoma kinase (Alk) and leading to a decrease of iridophore number in zebrafish [31], could disrupt white stripe formation. Treatments with TAE at 0.6 μM or 0.3 μM during the metamorphosis of A .…”

“…TAE684 (NVP-TAE684) (HY-10192, MedChem Express), a specific inhibitor of Ltk and Alk [31], was diluted in dimethylsulphoxyde (DMSO; Sigma-Aldrich Louis, MI, USA) to a final concentration of 6 mM. Larvae were treated from 5 until 18 dph in 0.005% DMSO with 0.3 μM or 0.6 μM TAE684 or without (controls).…”

A systems biology approach uncovers the core gene regulatory network governing iridophore fate choice from the neural crest

“…Sox10 plays a similar role in specification of both xanthophores and iridophores as well (Kelsh and Eisen, 2000;Dutton et al 2001). In the case of iridophores, as well as Sox10, the receptor tyrosine kinase Leukocyte tyrosine kinase (Ltk) plays a crucial role, with loss of function mutants lacking embryonic and adult iridophores, and constitutively activated Ltk signalling driving NCCs to adopt an iridophore fate (Lopes et al 2008;Rodrigues et al 2012;Fadeev et al 2016). We have shown that ltk expression appears to show two phases, one in early NC development which we propose represents a multipotent, chromatoblast-like progenitor, and a second in the definitive iridophore lineage (Lopes et al 2008).…”

Heterotypic interactions regulate cell shape and density during color pattern formation in zebrafish

“…Although it is clear that heterotypic interactions among all three types of pigment cells are necessary to generate the striped pattern (Frohnhöfer et al, 2013; Irion et al, 2014a; Singh et al, 2015), the outcome of these heterotypic interactions at the cellular level is not understood. In mutants where one type of pigment cells is absent [for example nacre/mitfa lacking melanophores (Lister et al, 1999), pfeffer/csf1ra lacking xanthophores (Parichy et al, 2000b) or shady/ltk lacking iridophores (Fadeev et al, 2016; Lopes et al, 2008)], only remnants of the normal stripe pattern are formed by the remaining two types of cells (see examples in Fig. 1).…”