Conservation of Pax 6 function and upstream activation by Notch signaling in eye development of frogs and flies
Conservation of Pax 6 function and upstream activation by Notch signaling in eye development of frogs and flies
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DOI：
10.1073/pnas.022626999
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发表时间：
2002-02-19
影响因子：
11.1
通讯作者：
Gehring, WJ
中科院分区：
文献类型：
--
作者：
Onuma, Y;Takahashi, S;Gehring, WJ
Pax 6功能缺失导致哺乳动物和昆虫无眼表型，果蝇和小鼠基因的异位表达导致果蝇异位眼的诱导，这提示Pax 6可能是眼形态发生的通用主控基因。在这里，我们报告了将果蝇Pax 6同源物（无眼和无眼双胞胎）的IRNA转移到脊椎动物胚胎中的互惠实验;即，2-和16-细胞阶段的早期非洲爪蟾胚胎。在这两种情况下，形成异位眼结构。为了了解指定眼睛形态发生的遗传程序，我们分析了启动眼睛发育的Pax 6表达的调控机制。在此之前，我们已经证明了Notch信号调节果蝇中eyeless和eyeless双生子的表达。在这里，我们表明，在非洲爪蟾，激活Notch信号也诱导眼相关的基因表达，包括Pax 6，在孤立的动物帽。在非洲爪蟾胚胎中，Notch信号的激活导致眼睛重复和近眼缺陷，这也是由无眼和无眼双胞胎的过度表达引起的。这些发现表明，在脊椎动物和无脊椎动物的基因调控级联是相似的。
Loss of Pax 6 function leads to an eyeless phenotype in both mammals and insects, and ectopic expression of both the Drosophila and the mouse gene leads to the induction of ectopic eyes in Drosophila, which suggested to us that Pax 6 might be a universal master control gene for eye morphogenesis. Here, we report the reciprocal experiment in which the IRNAs of the Drosophila Pax 6 homologs, eyeless and twin of eyeless, are transferred into a vertebrate embryo; i.e., early Xenopus embryos at the 2- and 16-cell stages. In both cases, ectopic eye structures are formed. To understand the genetic program specifying eye morphogenesis, we have analyzed the regulatory mechanisms of Pax 6 expression that initiates eye development. Previously, we have demonstrated that Notch signaling regulates the expression of eyeless and twin of eyeless in Drosophila. Here, we show that in Xenopus, activation of Notch signaling also induces eye-related gene expression, including Pax 6, in isolated animal caps. In Xenopus embryos, the activation of Notch signaling causes eye duplications and proximal eye defects, which are also induced by overexpression of eyeless and twin of eyeless. These findings indicate that the gene regulatory cascade is similar in vertebrates and invertebrates.