Distinct interactions of Sox5 and Sox10 in fate specification of pigment cells in medaka and zebrafish.
Distinct interactions of Sox5 and Sox10 in fate specification of pigment cells in medaka and zebrafish.
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DOI：
10.1371/journal.pgen.1007260
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发表时间：
2018-04
期刊：
影响因子：
4.5
通讯作者：
Hashimoto H
中科院分区：
文献类型：
--
作者：
Nagao Y;Takada H;Miyadai M;Adachi T;Seki R;Kamei Y;Hara I;Taniguchi Y;Naruse K;Hibi M;Kelsh RN;Hashimoto H
从多能祖细胞产生不同细胞类型的机制是正常发育的基础。色素细胞来源于多能神经嵴细胞，它们在硬骨鱼中的多样性为研究不同细胞类型的命运特化控制机制提供了一个很好的模型。斑马鱼有三种类型的色素细胞（黑色素细胞，虹膜细胞和黄色素细胞），而青鳉有四种（三种与斑马鱼共有，加上白细胞），这就提出了关于这些鱼中每种色素细胞类型的命运规范的保守机制的问题。我们以前已经表明，Sry相关的转录因子Sox 10是至关重要的命运规格的色素细胞在斑马鱼，和Sox 5促进黄色素和抑制leucophores在一个共享的黄色素/leucophore祖青鳉。采用TILLING、TALEN和CRISPR/Cas9技术，我们产生了青鳉和斑马鱼sox 5和sox 10突变体，并对其复合突变体表型进行了比较分析。我们表明，所有色素细胞的规格，除了leucophores，是依赖于Sox 10。Sox 10缺陷鱼中Sox 5的缺失部分挽救了斑马鱼中所有色素细胞的形成，以及青鳉中的黑素细胞和虹膜细胞，这表明Sox 5抑制了Sox 10依赖的这些色素细胞的形成，类似于它们在哺乳动物黑素细胞特化中的相互作用。与此相反，在青鳉，Sox 10的损失与Sox 5合作，提高了两个黄色素减少和leucophore增加Sox 5突变体。错误表达Sox 5的xanthophore/leucophore祖细胞增加xanthophore和减少leucophore青鳉。因此，Sox 5的功能在黄色素规范的模式不同青鳉（促进）和斑马鱼（抑制），这也是成鱼的情况。我们的研究结果揭示了令人惊讶的多样性，甚至Sox 5和Sox 10之间的相互作用的模式，规范的色素细胞类型的青少年和斑马鱼，并建议，这是有关的第四色素细胞类型的演变。个体细胞的命运如何从多能祖细胞中分化出来是发育和干细胞生物学中的一个基本问题。身体色素细胞来自多能祖细胞，但在斑马鱼中有三种类型的色素细胞（黑色素细胞，虹膜细胞和黄色素细胞），在青鳉中这些祖细胞形成四种（如斑马鱼，加上白细胞）。在这里，我们解决的机制是否产生每种细胞类型之间的两个物种是保守的。我们专注于两个关键的调控蛋白，Sox 5和Sox 10，我们以前表明，参与色素细胞的发展青鳉和斑马鱼，分别。我们实验比较这两种蛋白质如何相互作用，在这些鱼中的每个色素细胞谱系的调节发展。我们发现，所有色素细胞的发展，除了leucophores，是依赖于Sox 10，和Sox 5调制Sox 10活性拮抗在所有色素细胞在斑马鱼，黑色素细胞和虹膜细胞青鳉。令人惊讶的是，在青鳉中，Sox 5与Sox 10协同作用，以促进黄色素的命运，并抑制白色素的命运。我们的研究结果揭示了令人惊讶的多样性Sox 5和Sox 10如何相互作用，以管理青鳉和斑马鱼的色素细胞发育，并表明这可能与青鳉中新的leucophore色素细胞类型的进化有关。
Mechanisms generating diverse cell types from multipotent progenitors are fundamental for normal development. Pigment cells are derived from multipotent neural crest cells and their diversity in teleosts provides an excellent model for studying mechanisms controlling fate specification of distinct cell types. Zebrafish have three types of pigment cells (melanocytes, iridophores and xanthophores) while medaka have four (three shared with zebrafish, plus leucophores), raising questions about how conserved mechanisms of fate specification of each pigment cell type are in these fish. We have previously shown that the Sry-related transcription factor Sox10 is crucial for fate specification of pigment cells in zebrafish, and that Sox5 promotes xanthophores and represses leucophores in a shared xanthophore/leucophore progenitor in medaka. Employing TILLING, TALEN and CRISPR/Cas9 technologies, we generated medaka and zebrafish sox5 and sox10 mutants and conducted comparative analyses of their compound mutant phenotypes. We show that specification of all pigment cells, except leucophores, is dependent on Sox10. Loss of Sox5 in Sox10-defective fish partially rescued the formation of all pigment cells in zebrafish, and melanocytes and iridophores in medaka, suggesting that Sox5 represses Sox10-dependent formation of these pigment cells, similar to their interaction in mammalian melanocyte specification. In contrast, in medaka, loss of Sox10 acts cooperatively with Sox5, enhancing both xanthophore reduction and leucophore increase in sox5 mutants. Misexpression of Sox5 in the xanthophore/leucophore progenitors increased xanthophores and reduced leucophores in medaka. Thus, the mode of Sox5 function in xanthophore specification differs between medaka (promoting) and zebrafish (repressing), which is also the case in adult fish. Our findings reveal surprising diversity in even the mode of the interactions between Sox5 and Sox10 governing specification of pigment cell types in medaka and zebrafish, and suggest that this is related to the evolution of a fourth pigment cell type. How individual cell fates become specified from multipotent progenitors is a fundamental question in developmental and stem cell biology. Body pigment cells derive from a multipotent progenitor, but while in zebrafish there are three types of pigment cells (melanocytes, iridophores and xanthophores), in medaka these progenitors form four (as zebrafish, plus leucophores). Here, we address whether mechanisms generating each cell-type are conserved between the two species. We focus on two key regulatory proteins, Sox5 and Sox10, which we previously showed were involved in pigment cell development in medaka and zebrafish, respectively. We compare experimentally how the two proteins interact in regulating development of each of the pigment cell lineages in these fish. We show that development of all pigment cells, except leucophores, is dependent on Sox10, and that Sox5 modulates Sox10 activity antagonistically in all pigment cells in zebrafish, and melanocytes and iridophores in medaka. Surprisingly, in medaka, Sox5 acts co-operatively with Sox10 to promote xanthophore fate and to repress leucophore fate. Our findings reveal surprising diversity how Sox5 and Sox10 interact to govern pigment cell development in medaka and zebrafish, and suggest that this likely relates to the evolution of the novel leucophore pigment cell type in medaka.
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