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Drosophila TRAP230/240 are essential coactivators for Atonal in retinal neurogenesis

机译:果蝇TRAP230 / 240是视网膜神经再生中tonal的重要共激活剂。

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摘要

The TRAP (Thyroid hormone receptor associated proteins)/Mediator complex serves as a transcriptional coactivator. In Drosophila, Kohtalo (Kto) and Skuld (Skd), homologs of TRAP subunits, TRAP230 and TRAP240, respectively, are necessary for eye development. However, the transcriptional activators that require Kto and Skd have not been identified. Here we provide evidence that Kto and Skd are essential for the function of transcription factor Atonal (Ato) in spatial patterning of proneural clusters in the morphogenetic furrow. In the absence of Kto/Skd, Ato fails to induce its inhibitory target events such as EGFR signaling and Scabrous expression that result in ectopic Ato expression in the space between proneural groups. Kto/Skd are also required for positive Ato functions to induce Ato targets such as Ato itself and Senseless within the proneural clusters. We also show that Skd forms a protein complex with Ato in vivo. These data suggest that Kto/Skd act as essential coactivators for Ato expression during early retinal neurogenesis.
机译:TRAP(甲状腺激素受体相关蛋白)/介体复合物可作为转录共激活因子。在果蝇,科塔洛(Kto)和Skuld(Skd)中,分别需要TRAP亚基的同系物TRAP230和TRAP240对于眼睛发育是必需的。但是,尚未确定需要Kto和Skd的转录激活因子。在这里,我们提供的证据表明,Kto和Skd对于转录因子Atonal(Ato)在形态发生犁沟中前缘簇的空间模式中的功能至关重要。在没有Kto / Skd的情况下,Ato不能诱导其抑制性靶标事件,例如EGFR信号传导和Scabrous表达,从而导致异位Ato在前神经群之间的空间表达。积极的Ato功能还需要Kto / Skd来诱导Ato靶标,例如Ato本身和proneural簇内的Senseless。我们还显示Skd在体内与Ato形成蛋白质复合物。这些数据表明,在早期视网膜神经发生过程中,Kto / Skd充当Ato表达的必需共激活因子。

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