Coordinate control of synaptic-layer specificity and rhodopsins in photoreceptor neurons.
Coordinate control of synaptic-layer specificity and rhodopsins in photoreceptor neurons.
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DOI：
10.1038/nature07419
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发表时间：
2008-12-11
期刊：
影响因子：
64.8
通讯作者：
Zipursky, S. Lawrence
中科院分区：
文献类型：
--
作者：
Morey, Marta;Yee, Susan K.;Herman, Tory;Nern, Aljoscha;Blanco, Enrique;Zipursky, S. Lawrence
神经元如何建立特定的突触连接是神经生物学的核心问题。果蝇R7和R8感光轴突在大脑中不同突触层的靶向提供了一个模型，探索调节靶特异性的遗传程序。原则上，这可以通过介导突触伴侣之间的识别的细胞类型特异性分子来实现。或者，特异性也可以通过特定靶向分子的细胞类型特异性抑制来实现。在这里，我们表明，在R7神经元的靶向的一个关键步骤是R8靶向程序的主动抑制。抑制依赖于NF-YC，NF-Y（核因子Y）转录因子的亚基。在没有NF-YC的情况下，R7轴突终止于与R8轴突相同的层中。遗传实验表明，这仅仅是由于R8特异性转录因子无意义（Sens）在R7分化后期的去抑制。Sens足以控制R8靶向特异性，并且我们证明Sens直接结合到调节R8靶向特异性的R8特异性细胞表面蛋白Capricious（Caps）的转录起始上游的进化上保守的DNA序列。我们发现，R7靶向需要R7特异性转录因子Prospero（Pros）与NF-YC对R8靶向通路的抑制平行。先前的研究表明，Sens和Pros直接调节R8和R7中特异性视紫红质的表达。我们建议，使用相同的转录因子，以促进细胞类型的特异性表达的感觉受体和细胞表面蛋白调节突触靶特异性提供了一个简单的和一般的机制，以确保传输的感觉信息是由适当的专门的神经回路处理。
How neurons make specific synaptic connections is a central question in neurobiology. The targeting of the Drosophila R7 and R8 photoreceptor axons to different synaptic layers in the brain provides a model with which to explore the genetic programs regulating target specificity. In principle this can be accomplished by cell-type-specific molecules mediating the recognition between synaptic partners. Alternatively, specificity could also be achieved through cell-type-specific repression of particular targeting molecules. Here we show that a key step in the targeting of the R7 neuron is the active repression of the R8 targeting program. Repression is dependent on NF-YC, a subunit of the NF-Y (nuclear factor Y) transcription factor. In the absence of NF-YC, R7 axons terminate in the same layer as R8 axons. Genetic experiments indicate that this is due solely to the derepression of the R8-specific transcription factor Senseless (Sens) late in R7 differentiation. Sens is sufficient to control R8 targeting specificity and we demonstrate that Sens directly binds to an evolutionarily conserved DNA sequence upstream of the start of transcription of an R8-specific cell-surface protein, Capricious (Caps) that regulates R8 target specificity. We show that R7 targeting requires the R7-specific transcription factor Prospero (Pros) in parallel to repression of the R8targetingpathway by NF-YC. Previous studies demonstrated that Sens and Pros directly regulate the expression of specific rhodopsins in R8 and R7. We propose that the use of the same transcription factors to promote the cell-type-specific expression of sensory receptors and cell-surface proteins regulating synaptic target specificity provides a simple and general mechanism for ensuring that transmission of sensory information is processed by the appropriate specialized neural circuits.
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影响因子：
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