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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Evolutionary constraint on Otx2 neuroectoderm enhancers-deep conservation from skate to mouse and unique divergence in teleost
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Evolutionary constraint on Otx2 neuroectoderm enhancers-deep conservation from skate to mouse and unique divergence in teleost

机译：Otx2神经外胚层增强子的进化限制-从滑冰到小鼠的深层保护和硬骨鱼的独特发散

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摘要

Otx2 is a paired type homeobox gene that plays essential roles in each step and site of head development in vertebrates. In the mouse, Otx2 expression in the anterior neuroectoderm is regulated primarily by two distinct enhancers: anterior neuroectoderm (AN) and forebrain/midbrain (FM) enhancers at 92 kb and 75 kb 5' of the Otx2 locus, respectively. The AN enhancer has activity in the entire anterior neuroectoderm at headfold and early somite stages, whereas the FM enhancer is subsequently active in the future caudal forebrain and midbrain ectoderm. in tetrapods, both AN and FM enhancers are conserved, whereas the AN region is missing in teleosts, despite overt Otx2 expression in the anterior neuroectoderm. Here, we show that zebrafish and fugu FM regions drive expression not only in the forebrain and midbrain but also in the anterior neuroectoderm at headfold stage. The analysis of coela-canth and skate genomic Otx2 orthologues suggests that the utilization of the two enhancers, AN and FM, is an ancestral condition. In contrast, the AN enhancer has been specifically lost in the teleost lineage with a compensatory establishment of AN activity within the FM enhancer. Furthermore, the AN activity in the fish FM enhancer was established by recruiting upstream factors different from those that direct the tetrapod AN enhancer, yet zebrafish FM enhancer is active in both mouse and zebrafish anterior neuroectoderm at the headfold stage.
机译：Otx2是一个配对的同源盒基因，在脊椎动物头部发育的每个步骤和部位中都起着至关重要的作用。在小鼠中，前神经外胚层中Otx2的表达主要受两种不同的增强子调控：分别位于Otx2基因座的92 kb和75 kb 5'处的前神经外胚层（AN）和前脑/中脑（FM）增强子。 AN增强剂在头褶和早期so突阶段在整个前神经外胚层中具有活性，而FM增强剂随后在未来的尾前脑和中脑外胚层中具有活性。在四足动物中，AN和FM增强子均被保守，而硬骨鱼中AN区缺失，尽管前神经外胚层中Otx2表达明显。在这里，我们显示斑马鱼和河豚FM区域不仅在前脑和中脑而且在头折阶段在前神经外胚层中驱动表达。对腔棘鱼和滑冰基因组Otx2直向同源物的分析表明，使用两种增强子AN和FM是祖传条件。相比之下，AN增强剂由于在FM增强剂中补偿性建立了AN活性而在硬骨症谱系中特别丢失。此外，鱼FM增强子中的AN活性是通过募集不同于指导四足动物AN增强子的上游因素而建立的，而斑马鱼FM增强子在头折期在小鼠和斑马鱼前神经外胚层中均具有活性。

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