MAPK target sites of eyes absent are not required for eye development or survival in Drosophila.
MAPK target sites of eyes absent are not required for eye development or survival in Drosophila.
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DOI：
10.1371/journal.pone.0050776
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Mardon G
中科院分区：
文献类型：
--
作者：
Jusiak B;Abulimiti A;Haelterman N;Chen R;Mardon G
缺眼 (Eya) 是一种高度保守的转录辅因子和蛋白磷酸酶，在果蝇眼睛发育和生存中发挥着重要作用。使用 cDNA 转基因的异位眼诱导测定表明，丝裂原激活蛋白激酶 (MAPK) 通过在两个共有靶位点 S402 和 S407 上磷酸化 Eya 来激活 Eya，并且这种激活增强了 Eya 驱动眼形成的能力。然而，这种机制从未在正常眼睛发育中得到测试。在当前的研究中，我们生成了一系列基因组拯救转基因，以研究 Eya 内这两个 MAPK 靶位点的功能丧失和功能获得突变如何影响果蝇的存活和正常眼睛形成：eya+GR，野生型对照； eyaSAGR，两个目标残基缺乏磷酸化； eyaSDEGR，其在相同的两个残基处含有拟磷氨基酸。与之前异位眼发育的研究相反，所有经过测试的 eya 基因组转基因都同样有效地挽救了眼睛的形成和存活。我们得出的结论是，与异位眼的形成相反，MAPK 介导的 Eya 在 S402 和 S407 上的磷酸化在正常发育中不起作用。这是第一项针对果蝇的研究，旨在评估同一基因的基因组拯救和基于异位 cDNA 的过度表达之间的结果差异。这些发现表明，类似的基因组拯救策略可能有助于重新评估其他长期存在的果蝇发育模型。
Eyes absent (Eya) is a highly conserved transcription cofactor and protein phosphatase that plays an essential role in eye development and survival in Drosophila. Ectopic eye induction assays using cDNA transgenes have suggested that mitogen activated protein kinase (MAPK) activates Eya by phosphorylating it on two consensus target sites, S402 and S407, and that this activation potentiates the ability of Eya to drive eye formation. However, this mechanism has never been tested in normal eye development. In the current study, we generated a series of genomic rescue transgenes to investigate how loss- and gain-of-function mutations at these two MAPK target sites within Eya affect Drosophila survival and normal eye formation: eya+GR, the wild-type control; eyaSAGR, which lacks phosphorylation at the two target residues; and eyaSDEGR, which contains phosphomimetic amino acids at the same two residues. Contrary to the previous studies in ectopic eye development, all eya genomic transgenes tested rescue both eye formation and survival equally effectively. We conclude that, in contrast to ectopic eye formation, MAPK-mediated phosphorylation of Eya on S402 and S407 does not play a role in normal development. This is the first study in Drosophila to evaluate the difference in outcomes between genomic rescue and ectopic cDNA-based overexpression of the same gene. These findings indicate similar genomic rescue strategies may prove useful for re-evaluating other long-standing Drosophila developmental models.
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影响因子：
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