Six3 activation of Pax6 expression is essential for mammalian lens induction and specification
Six3 activation of Pax6 expression is essential for mammalian lens induction and specification
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DOI：
10.1038/sj.emboj.7601398
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发表时间：
2006-11-15
期刊：
影响因子：
11.4
通讯作者：
Oliver, Guillermo
中科院分区：
文献类型：
--
作者：
Liu, Wei;Lagutin, Oleg V.;Oliver, Guillermo
同形盒基因Six3调节前脑发育。在这里，我们表明Six3对于晶状体的形成也是至关重要的。假定晶状体外胚层（PLE）中小鼠Six3的条件缺失破坏了晶状体的形成。在最严重的情况下，晶状体诱导和规格有缺陷，晶状体基板和晶状体缺失。在six3突变体胚胎中，Pax6被下调，Sox2在晶状体胎盘前外胚层中缺失。通过ChIP、电泳迁移率测定和荧光素酶报告基因测定，我们确定Six3激活Pax6和Sox2的表达。小鼠Six3在鸡胚中的错表达促进了外胚层Pax6表达域的异位扩增。我们的研究结果将Six3定位于导致晶状体形成的调控途径的顶端。我们得出结论，Six3直接激活PLE中的Pax6和Sox2，并自主调节哺乳动物晶状体诱导的早期阶段。
The homeobox gene Six3 regulates forebrain development. Here we show that Six3 is also crucial for lens formation. Conditional deletion of mouse Six3 in the presumptive lens ectoderm (PLE) disrupted lens formation. In the most severe cases, lens induction and specification were defective, and the lens placode and lens were absent. In Six3-mutant embryos, Pax6 was downregulated, and Sox2 was absent in the lens preplacodal ectoderm. Using ChIP, electrophoretic mobility shift assay, and luciferase reporter assays, we determined that Six3 activates Pax6 and Sox2 expression. Misexpression of mouse Six3 into chick embryos promoted the ectopic expansion of the ectodermal Pax6 expression domain. Our results position Six3 at the top of the regulatory pathway leading to lens formation. We conclude that Six3 directly activates Pax6 and probably also Sox2 in the PLE and regulates cell autonomously the earliest stages of mammalian lens induction.