Gain-of-function screen identifies a role of the Src64 oncogene in Drosophila mushroom body development
Gain-of-function screen identifies a role of the Src64 oncogene in Drosophila mushroom body development
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DOI：
10.1002/neu.10277
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发表时间：
2003-12-01
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影响因子：
--
通讯作者：
Dura, JM
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作者：
Nicolaï, M;Lasbleiz, C;Dura, JM
蘑菇体（MB）是果蝇大脑中对记忆至关重要的亚结构。目前，MB的解剖是相当好的描述相比，其他脑区，和阐明MB神经元的发育和投射模式的遗传控制将是重要的了解他们的功能。我们进行了功能获得性筛选，以确定参与MB发展的基因。我们通过将2407 GAL 4驱动的UY元件系与含有MB GAL 4源和UAS-GFP元件的系杂交来驱动MB神经元中的基因表达，并寻找MB结构中的缺陷。我们已经从分子水平鉴定了26个阳性UY插入的基因组区域，并发现了18个表现出成人MB功能获得性表型的潜在基因。由这些候选基因编码的蛋白质包括，以及具有未知功能的基因，转录因子（例如，tramtrack）、nanos RNA结合蛋白、微管切断蛋白、囊泡运输蛋白、轴突导向受体和Src 64胞质蛋白酪氨酸激酶。这些基因涉及神经元细胞生物学的关键特征。在三种情况下，tramtrack，nanos和Src 64，我们表明，开放的阅读框直接位于下游的UY P元件确实是表达的靶基因。ttk和Src 64的功能丧失突变导致MB表型，证明这些基因参与MB发育的遗传控制。此外，Src 64在这里显示，以细胞自主的方式发挥作用，并可能与以前确定的linotte/出轨受体酪氨酸激酶MB的发展。(C)2003 Wiley Periodicals，Inc.
Mushroom bodies (MB) are substructures in the Drosophila brain that are essential for memory. At present, MB anatomy is rather well described when compared to other brain areas, and elucidation of the genetic control of the development and projection patterns of MB neurons will be important to the understanding of their functions. We have performed a gain-of-function screen in order to identify genes that are involved in MB development. We drove expression of genes in MB neurons by crossing 2407 GAL4-driven UY element lines to lines containing an MB GAL4 source and UAS-GFP elements, and looked for defects in the MB structure. We have molecularly identified the genomic regions adjacent to the 26 positive UY insertions and found 18 potential genes that exhibit adult MB gain-of-function phenotypes. The proteins encoded by these candidate genes include, as well as genes with yet unknown function, transcription factors (e.g., tramtrack), nanos RNA-binding protein, microtubule-severing protein, vesicle trafficking proteins, axon guidance receptor, and the Src64 cytoplasmic protein tyrosine kinase. These genes are involved in key features of neuron cell biology. In three cases, tramtrack, nanos, and Src64, we show that the open reading frame located directly downstream of the UY P element is indeed the expressed target gene. Loss-of-function mutations of both ttk and Src64 lead to MB phenotypes proving that these genes are involved in the genetic control of MB development. Moreover, Src64 is shown here to act in a cell-autonomous fashion and is likely to interact with the previously-identified linotte/derailed receptor tyrosine kinase in MB development. (C) 2003 Wiley Periodicals, Inc.