Fadeev Andrey, Krauss Jana, Singh Ajeet Pratap, Nüsslein-Volhard Christiane
Max-Planck-Institut für Entwicklungsbiologie, Tübingen, Germany.
Pigment Cell Melanoma Res. 2016 May;29(3):284-96. doi: 10.1111/pcmr.12454.
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.
斑马鱼的条纹图案源于三种色素细胞类型之间的相互作用，即黑色的黑素细胞、黄色的黄色素细胞和银色的虹彩细胞，这使得它成为研究体内图案形成的一个有价值的模型。有人提出，虹彩细胞的增殖、扩散和细胞形状转变在条纹形成过程中起重要作用；然而，其潜在的分子机制仍知之甚少。利用白细胞酪氨酸激酶（ltk）的功能获得和功能丧失等位基因以及药理学抑制剂方法，我们表明Ltk特异性调节虹彩细胞的建立、增殖和存活。shady/ltk突变体缺乏虹彩细胞，并表现出异常的身体条纹图案。月光石突变体ltk（mne）表现出异位虹彩细胞，表明突变型Ltk活性过高。显性ltk（mne）等位基因在激酶结构域的保守位置携带一个错义突变，该突变与哺乳动物的神经母细胞瘤高度相关。嵌合分析表明Ltk在通过同型竞争调节虹彩细胞增殖方面具有新的生理作用。
