Sequential actions of Pax3 and Pax7 drive xanthophore development in zebrafish neural crest.
Sequential actions of Pax3 and Pax7 drive xanthophore development in zebrafish neural crest.
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DOI：
10.1016/j.ydbio.2008.02.058
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发表时间：
2008-05-15
影响因子：
2.7
通讯作者：
Hughes, Simon M.
中科院分区：
文献类型：
--
作者：
Minchin, James E. N.;Hughes, Simon M.
关键词：
Pax3/7基因家族在神经嵴形成过程中具有基础性和保守性的作用。在人类中，PAX3突变导致Waardenburg综合征，而小鼠PAX3对色素形成至关重要。然而，目前尚不清楚Pax3在神经嵴中的确切功能。在斑马鱼神经嵴发育早期，pax3先于其他pax3/7成员（包括重复的pax3b、pax7和pax7b基因）表达。反义morpholino寡核苷酸敲低Pax3蛋白会导致黄嘌呤载体命运规范缺陷，导致树干完全消融。其他色素谱系被指定和区分。作为叶黄素丧失的结果，叶黄素谱系的标志pax7的表达在神经嵴中减少。Pax7蛋白的Morpholino敲低表明Pax7本身对于叶黄素的命运规范是不可缺少的，尽管黄色色素沉着减少了。Pax3减少后的黄细胞损失与黑素细胞分化的延迟相关，随后黑素细胞显著增加，提示在染色质前体或干细胞中由Pax3驱动的命运开关。对其他神经嵴衍生物的分析表明，在缺乏Pax3的情况下，肠神经系统从一开始就被消融。因此，斑马鱼需要Pax3来确定神经嵴、黄细胞和肠神经元两个特定谱系。
The Pax3/7 gene family has a fundamental and conserved role during neural crest formation. In people, PAX3 mutation causes Waardenburg syndrome, and murine Pax3 is essential for pigment formation. However, it is unclear exactly how Pax3 functions within the neural crest. Here we show that pax3 is expressed before other pax3/7 members, including duplicated pax3b, pax7 and pax7b genes, early in zebrafish neural crest development. Knockdown of Pax3 protein by antisense morpholino oligonucleotides results in defective fate specification of xanthophores, with complete ablation in the trunk. Other pigment lineages are specified and differentiate. As a consequence of xanthophore loss, expression of pax7, a marker of the xanthophore lineage, is reduced in neural crest. Morpholino knockdown of Pax7 protein shows that Pax7 itself is dispensable for xanthophore fate specification, although yellow pigmentation is reduced. Loss of xanthophores after reduction of Pax3 correlates with a delay in melanoblast differentiation followed by significant increase in melanophores, suggestive of a Pax3-driven fate switch within a chromatophore precursor or stem cell. Analysis of other neural crest derivatives reveals that, in the absence of Pax3, the enteric nervous system is ablated from its inception. Therefore, Pax3 in zebrafish is required for specification of two specific lineages of neural crest, xanthophores and enteric neurons.
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