Lhx2 mediates the activity of Six3 in zebrafish forebrain growth
Lhx2 mediates the activity of Six3 in zebrafish forebrain growth
复制标题
DOI：
10.1016/j.ydbio.2005.09.023
复制
发表时间：
2005-11-15
影响因子：
2.7
通讯作者：
Okamoto, H
中科院分区：
文献类型：
--
作者：
Ando, H;Kobayashi, M;Okamoto, H
在脊椎动物的大脑中，端脑显示出最大程度的大小变化。了解调节端脑生长的遗传级联对于我们理解正常人类大脑的进化如何支持这种大小变化至关重要。在这里，我们提出了一个简单而快速的方法来分析这种级联反应，结合笼mRNA技术和使用反义吗啉代寡核苷酸在斑马鱼胚胎。Lhx2，一种LIM同源结构域蛋白，和Six3s（Six3b和Six3a），另一种同源结构域蛋白，在前脑发育的早期表现出非常相似的表达模式，并且已知这些参与大脑这一部分的生长。由于细胞增殖受损，six3b和six3a双morphant（six3 morphant）胚胎的端脑大小显着减少。头部特异性过表达Lhx2的光激活的笼状lhx2 mRNA完全拯救了这种大小的减少，而类似的头部特异性激活Six3b不能拯救敲低效应的lhx2。在青鳉胚胎的前脑中，Six3通过从Cdt1中隔离Geminin来促进细胞增殖，Cdt1是复制前复合物组装中的关键组分。我们的研究结果表明，Lhx2可能介导的替代或平行的途径，通过Six3控制细胞增殖的发育中的前脑。(C)2005年爱思唯尔公司All rights reserved.
The telencephalon shows the greatest degree of size variation in the vertebrate brain. Understanding the genetic cascade that regulates telencephalon growth is crucial to our understanding of how evolution of the normal human brain has supported such a variation in size. Here, we present a simple and quick approach to analyze this cascade that combines caged-mRNA technology and the use of antisense morpholino oligonucleotides in zebrafish embryos. Lhx2, a LIM-homeodomain protein, and Six3s (Six3b and Six3a), another homeodomain proteins, show very similar expression patterns early in forebrain development, and these are known to be involved in the growth of this part of the brain. The telencephalon of six3b and six3a double morphant (six3 morphant) embryos is markedly reduced in size due to impaired cellular proliferation. Head-specific overexpression of Lhx2 by photoactivation of a caged-lhx2 mRNA completely rescued this size reduction, whereas similar head-specific activation of Six3b could not rescue the knockdown effect of lhx2. In the forebrain of medaka embryos, Six3 facilitates cellular proliferation by sequestration of Geminin from Cdt1, a key component in the assembly of the prereplication complex. Our results suggest that Lhx2 may mediate an alternative or parallel pathway for control of cellular proliferation in the developing forebrain via Six3. (C) 2005 Elsevier Inc. All rights reserved.