Possible involvement of SINEs in mammalian-specific brain formation
Possible involvement of SINEs in mammalian-specific brain formation
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DOI：
10.1073/pnas.0709398105
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发表时间：
2008-03-18
影响因子：
11.1
通讯作者：
Okada, Norihiro
中科院分区：
文献类型：
--
作者：
Sasaki, Takeshi;Nishihara, Hidenori;Okada, Norihiro
反转录子是高等脊椎动物基因组的主要组成部分，如短穿插元件（SINEs）和长穿插元件（LINES）。虽然有许多逆转录子获得功能的例子，但没有一个涉及特定分类群体的形态创新。我们之前描述了一个sin家族，amnsnine1，其成员构成了哺乳动物基因组中保守非编码元件（CNEs）的一部分。我们认为这个家族在哺乳动物祖先中逆转录后获得了基因组功能或被排除在外。在这里，我们鉴定了53个新的AmnSINE1位点，并改进了124个总位点，其中两个位点进一步分析。通过小鼠增强子实验，我们发现一个sin位点AS071，距离FGF8基因（成纤维细胞生长因子8）178 kbp，是一个增强子，它在发育中的前脑的两个区域，即间脑和下丘脑中重述FGF8的表达。我们的功能获得分析显示，间脑中FGF8的表达控制丘脑核的模式，而丘脑核是新皮层的中继中心，这表明FGF8在哺乳动物特异性前脑模式中起作用。此外，我们证明了AS021位点，位于SATB2基因392 kbp处，控制着侧端脑的基因表达，而侧端脑被认为是发育过程中的信号传导中心。这些结果表明，sin在哺乳动物神经网络的发育中起着重要作用，其中一部分是随着amnsnine1在一个共同的哺乳动物祖先中的表达而启动的。
Retroposons, such as short interspersed elements (SINEs) and long interspersed elements (LINES), are the major constituents of higher vertebrate genomes. Although there are many examples of retroposons' acquiring function, none has been implicated in the morphological innovations specific to a certain taxonomic group. We previously characterized a SINE family, AmnSINE1, members of which constitute a part of conserved noncoding elements (CNEs) in mammalian genomes. We proposed that this family acquired genomic functionality or was exapted after retropositioning in a mammalian ancestor. Here we identified 53 new AmnSINE1 loci and refined 124 total loci, two of which were further analyzed. Using a mouse enhancer assay, we demonstrate that one SINE locus, AS071, 178 kbp from the gene FGF8 (fibroblast growth factor 8), is an enhancer that recapitulates FGF8 expression in two regions of the developing forebrain, namely the diencephalon and the hypothalamus. Our gain-of-function analysis revealed that FGF8 expression in the diencephalon controls patterning of thalamic nuclei, which act as a relay center of the neocortex, suggesting a role for FGF8 in mammalian-specific forebrain patterning. Furthermore, we demonstrated that the locus, AS021, 392 kbp from the gene SATB2, controls gene expression in the lateral telencephalon, which is thought to be a signaling center during development. These results suggest important roles for SINEs in the development of the mammalian neuronal network, a part of which was initiated with the exaptation of AmnSINE1 in a common mammalian ancestor.