Otx2 expression in anterior neuroectoderm and forebrain/midbrain is directed by more than six enhancers.
Otx2 expression in anterior neuroectoderm and forebrain/midbrain is directed by more than six enhancers.
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DOI：
10.1016/j.ydbio.2014.01.011
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发表时间：
2014-03
影响因子：
2.7
通讯作者：
D. Kurokawa;Tomomi Ohmura;Yusuke Sakurai;Ken-ichi Inoue;Y. Suda;S. Aizawa
中科院分区：
文献类型：
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作者：
D. Kurokawa;Tomomi Ohmura;Yusuke Sakurai;Ken-ichi Inoue;Y. Suda;S. Aizawa
在头部发育的每个阶段，Otx2在每个部位都扮演着重要的角色。我们先前发现AN1增强子在E8.5之前的神经板期的前神经外胚层中表达，FM1增强子在75 kb的5‘上游和FM2增强子在122 kb的3’下游表达，在E8.5之后的前脑/中脑(FM)中表达。本研究发现了位于上游88kb的第二个增强子(AN2)；AN2增强子还概括了内源性Otx2在脉络丛、皮质下摆和脉络膜顶的表达。然而，增强子突变体表明存在另一种增强子.该研究还发现了上游153kb的第三个FM增强子(FM3)。因此，Otx2在前神经外胚层和前脑/中脑中的表达受到远离编码区的6个以上增强子的调控。已鉴定的增强子在脊椎动物中具有差异保守性；在E8.5之后的脑泡期，AN增强子在尾侧前脑和中脑中没有活性；在E8.5之前的神经板期，在前神经外胚层中没有任何FM增强子具有活性。
Otx2plays essential roles in each site at each step of head development. We previously identified the AN1 enhancer at 91 kb 5' upstream for theOtx2expressions in anterior neuroectoderm (AN) at neural plate stage before E8.5, and the FM1 enhancer at 75 kb 5' upstream and the FM2 enhancer at 122 kb 3' downstream for the expression in forebrain/midbrain (FM) at brain vesicle stage after E8.5. The present study identified a second AN enhancer (AN2) at 88 kb 5' upstream; the AN2 enhancer also recapitulates the endogenousOtx2expression in choroid plexus, cortical hem and choroidal roof. However, the enhancer mutants indicated the presence of another AN enhancer. The study also identified a third FM enhancer (FM3) at 153 kb 5' upstream. Thus, theOtx2expressions in anterior neuroectoderm and forebrain/midbrain are regulated by more than six enhancers located far from the coding region. The enhancers identified are differentially conserved among vertebrates; none of the AN enhancers has activities in caudal forebrain and midbrain at brain vesicle stage after E8.5, nor do any of the FM enhancers in anterior neuroectoderm at neural plate stage before E8.5.