Direct control of the proneural gene atonal by retinal determination factors during Drosophila eye development.
Direct control of the proneural gene atonal by retinal determination factors during Drosophila eye development.
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DOI：
10.1016/j.ydbio.2007.11.017
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发表时间：
2008-01
影响因子：
2.7
通讯作者：
Miho Tanaka‐Matakatsu;W. Du
中科院分区：
文献类型：
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作者：
Miho Tanaka‐Matakatsu;W. Du
果蝇细胞中神经元身份的确定依赖于原神经基因的准确表达。前神经基因无调（ato）编码光感受器和弦音器官形成所需的碱性HLH蛋白。ato在成虫盘中的初始表达受到位于其开放阅读框3 '端的序列的调节。在这份报告中，我们表明，在不同的成虫盘的初始ato转录是由不同的3′顺式调控序列。眼特异的ato 3′顺式调控序列由两个不同的元件组成，我们称之为2.8PB和3.6BP，它们在眼发育的不同阶段调控ato的转录。2.8PB增强子包含视网膜决定（RD）因子Sine oculis（So）的高度保守的共有结合位点。该So结合位点的突变消除了2.8PB增强子活性。此外，RD因子So和Eyes absence（Eya）是2.8PB增强子活性所需的，并且可以诱导异位2.8PB报告基因表达。相反，异位Dpp信号传导不足以诱导ato 3′增强子激活，但可以诱导RD因子Dachshund（Dac）水平升高，并与So和Eya协同增加ato 3′增强子活性。这些结果表明RD因子调节ato表达的直接机制，并提示Dpp在ato 3′增强子激活中的重要作用是调节RD因子的水平。
The determination of neuronal identity in Drosophila cells depends on the accurate expression of proneural genes. The proneural gene atonal (ato) encodes a basic-HLH protein required for photoreceptor and chordotonal organ formation. The initial expression of ato in imaginal discs is regulated by sequences that lie 3′ to its open reading frame. In this report, we show that the initial ato transcription in different imaginal discs is regulated by distinct 3′ cis-regulatory sequences. The eye-specific ato 3′ cis-regulatory sequence consists of two distinct elements we term 2.8PB and 3.6BP that regulate ato transcription during different stages of eye development. The 2.8PB enhancer contains a highly conserved consensus binding site for the retinal determination (RD) factor Sine oculis (So). Mutation of this So binding site abolishes 2.8PB enhancer activity. Furthermore the RD factors So and Eyes absent (Eya) are required for 2.8PB enhancer activity and can induce ectopic 2.8PB reporter expression. In contrast, ectopic Dpp signaling is not sufficient to induce ato 3′ enhancer activation but can induce increased levels of RD factor Dachshund (Dac) and synergize with So and Eya to increase ato 3′ enhancer activity. These results demonstrate a direct mechanism by which the RD factors regulate ato expression and suggest an important role of Dpp in the activation of ato 3′ enhancer is to regulate the levels of RD factors.