Department of Biology, University of Washington, Seattle, WA, USA.
PLoS Genet. 2013 May;9(5):e1003561. doi: 10.1371/journal.pgen.1003561. Epub 2013 May 30.
Skin pigment patterns of vertebrates are a classic system for understanding fundamental mechanisms of morphogenesis, differentiation, and pattern formation, and recent studies of zebrafish have started to elucidate the cellular interactions and molecular mechanisms underlying these processes. In this species, horizontal dark stripes of melanophores alternate with light interstripes of yellow or orange xanthophores and iridescent iridophores. We showed previously that the highly conserved zinc finger protein Basonuclin-2 (Bnc2) is required in the environment in which pigment cells reside to promote the development and maintenance of all three classes of pigment cells; bnc2 mutants lack body stripes and interstripes. Previous studies also revealed that interactions between melanophores and xanthophores are necessary for organizing stripes and interstripes. Here we show that bnc2 promotes melanophore and xanthophore development by regulating expression of the growth factors Kit ligand a (Kitlga) and Colony stimulating factor-1 (Csf1), respectively. Yet, we found that rescue of melanophores and xanthophores was insufficient for the recovery of stripes in the bnc2 mutant. We therefore asked whether bnc2-dependent iridophores might contribute to stripe and interstripe patterning as well. We found that iridophores themselves express Csf1, and by ablating iridophores in wild-type and mutant backgrounds, we showed that iridophores contribute to organizing both melanophores and xanthophores during the development of stripes and interstripes. Our results reveal an important role for the cellular environment in promoting adult pigment pattern formation and identify new components of a pigment-cell autonomous pattern-generating system likely to have broad implications for understanding how pigment patterns develop and evolve.
脊椎动物的皮肤色素模式是理解形态发生、分化和模式形成基本机制的经典系统，最近对斑马鱼的研究已经开始阐明这些过程背后的细胞相互作用和分子机制。在这个物种中，黑色素细胞的水平暗条纹与黄色或橙色的黄色素细胞和彩虹色的虹彩细胞的浅色间条纹交替出现。我们之前表明，高度保守的锌指蛋白 Basonuclin-2（Bnc2）在色素细胞所在的环境中是必需的，以促进所有三类色素细胞的发育和维持；bnc2 突变体缺乏身体条纹和间条纹。先前的研究还揭示了黑色素细胞和黄色素细胞之间的相互作用对于组织条纹和间条纹是必要的。在这里，我们表明 bnc2 通过分别调节生长因子 Kit 配体 a（Kitlga）和集落刺激因子-1（Csf1）的表达来促进黑色素细胞和黄色素细胞的发育。然而，我们发现 bnc2 对黑色素细胞和黄色素细胞的拯救不足以恢复 bnc2 突变体中的条纹。因此，我们询问 bnc2 依赖的虹彩细胞是否也可能有助于条纹和间条纹的图案形成。我们发现虹彩细胞本身表达 Csf1，并且通过在野生型和突变体背景下消融虹彩细胞，我们表明虹彩细胞有助于在条纹和间条纹的发育过程中组织黑色素细胞和黄色素细胞。我们的结果揭示了细胞环境在促进成年色素模式形成中的重要作用，并确定了一个色素细胞自主模式生成系统的新成分，这可能对理解色素模式如何发育和进化具有广泛的意义。
