Orthodenticle Is Required for the Expression of Principal Recognition Molecules That Control Axon Targeting in the Drosophila Retina.
Orthodenticle Is Required for the Expression of Principal Recognition Molecules That Control Axon Targeting in the Drosophila Retina.
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DOI：
10.1371/journal.pgen.1005303
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发表时间：
2015-06
期刊：
影响因子：
4.5
通讯作者：
Pichaud F
中科院分区：
文献类型：
--
作者：
Mencarelli C;Pichaud F
Parallel processing of neuronal inputs relies on assembling neural circuits into distinct synaptic-columns and layers. This is orchestrated by matching recognition molecules between afferent growth cones and target areas. Controlling the expression of these molecules during development is crucial but not well understood. The developing Drosophila visual system is a powerful genetic model for addressing this question. In this model system, the achromatic R1-6 photoreceptors project their axons in the lamina while the R7 and R8 photoreceptors, which are involved in colour detection, project their axons to two distinct synaptic-layers in the medulla. Here we show that the conserved homeodomain transcription factor Orthodenticle (Otd), which in the eye is a main regulator of rhodopsin expression, is also required for R1-6 photoreceptor synaptic-column specific innervation of the lamina. Our data indicate that otd function in these photoreceptors is largely mediated by the recognition molecules flamingo (fmi) and golden goal (gogo). In addition, we find that otd regulates synaptic-layer targeting of R8. We demonstrate that during this process, otd and the R8-specific transcription factor senseless/Gfi1 (sens) function as independent transcriptional inputs that are required for the expression of fmi, gogo and the adhesion molecule capricious (caps), which govern R8 synaptic-layer targeting. Our work therefore demonstrates that otd is a main component of the gene regulatory network that regulates synaptic-column and layer targeting in the fly visual system. Establishing neural circuits during brain development relies on the ability for neurons to find their appropriate targets, a task that depends on recognition molecules whose expression must be tightly controlled. Very little is known of the factors that control the expression of these molecules. Here we have used the genetically amenable fly retina to address this issue. We identify Orthodenticle, a protein involved in mammalian brain development, as a main component of a new genetic cascade controlling the expression of recognition molecules that govern the wiring of the fly retina. Our work raises the issue that Orthodenticle might play a similar role in mammals. It also sheds new light on the genetic basis for wiring a model neural circuit during development.
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