Xenopus mutant reveals necessity of rax for specifying the eye field which otherwise forms tissue with telencephalic and diencephalic character.
Xenopus mutant reveals necessity of rax for specifying the eye field which otherwise forms tissue with telencephalic and diencephalic character.
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DOI：
10.1016/j.ydbio.2014.09.004
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发表时间：
2014-11-15
影响因子：
2.7
通讯作者：
Grainger, Robert M.
中科院分区：
文献类型：
--
作者：
Fish, Margaret B.;Nakayama, Takuya;Fisher, Marilyn;Hirsch, Nicolas;Cox, Amanda;Reeder, Rollin;Carruthers, Samantha;Hall, Amanda;Stemple, Derek L.;Grainger, Robert M.
视网膜前同源盒基因（rax）编码脊椎动物眼睛发育所必需的转录因子。rax转录起始于非洲爪蟾原肠胚形成的末期，并且是指定前神经板和视网膜的调节网络的关键部分。我们在这里描述了热带爪蟾rax突变体，第一个突变体的详细分析，从反向遗传筛选。与其他脊椎动物一样，这种无义突变导致无眼动物，并且是致命的近变态。在这些突变体中，通常注定形成视网膜的组织形成具有间脑和端脑特征的组织。这意味着rax的一个关键作用，除了定义视野，是在防止替代前脑身份。我们的数据强调，大脑和视网膜区域不是由中期原肠胚阶段，而是由神经板阶段决定的。在突变体中早期基因表达的RNA-Seq分析和原位杂交测定显示，几个关键的眼场转录因子（例如pax 6，lhx 2和six 6）不依赖于rax活性通过神经形成。然而，这些分析确定了其他基因在突变推定视网膜组织中上调或下调。在rax突变体RNA-seq分析中出现上调的两个特别感兴趣的神经模式基因是hesx 1和fezf 2。以前不知道这些基因是由rax调控的。rax的正常功能是通过间接机制在野生型胚胎的假定视网膜区域部分抑制其表达，从而解释rax突变体中的明显上调。使用针对hesx 1和fezf 2的反义吗啉代寡核苷酸的敲除实验表明，在rax突变体中，未能抑制这两个基因有助于假定的视网膜组织转化为非视网膜前脑身份。
The retinal anterior homeobox (rax) gene encodes a transcription factor necessary for vertebrate eye development. rax transcription is initiated at the end of gastrulation in Xenopus, and is a key part of the regulatory network specifying anterior neural plate and retina. We describe here a Xenopus tropicalis rax mutant, the first mutant analyzed in detail from a reverse genetic screen. As in other vertebrates, this nonsense mutation results in eyeless animals, and is lethal peri-metamorphosis. Tissue normally fated to form retina in these mutants instead forms tissue with characteristics of diencephalon and telencephalon. This implies that a key role of rax, in addition to defining the eye field, is in preventing alternative forebrain identities. Our data highlight that brain and retina regions are not determined by the mid-gastrula stage but are by the neural plate stage. An RNA-Seq analysis and in situ hybridization assays for early gene expression in the mutant revealed that several key eye field transcription factors (e.g. pax6, lhx2 and six6) are not dependent on rax activity through neurulation. However, these analyses identified other genes either up- or down-regulated in mutant presumptive retinal tissue. Two neural patterning genes of particular interest that appear up-regulated in the rax mutant RNA-seq analysis are hesx1 and fezf2. These genes were not previously known to be regulated by rax. The normal function of rax is to partially repress their expression by an indirect mechanism in the presumptive retina region in wildtype embryos, thus accounting for the apparent up-regulation in the rax mutant. Knock-down experiments using antisense morpholino oligonucleotides directed against hesx1 and fezf2 show that failure to repress these two genes contributes to transformation of presumptive retinal tissue into non-retinal forebrain identities in the rax mutant.
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通讯作者：
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