Phr1 regulates retinogeniculate targeting independent of activity and ephrin-A signalling
Phr1 regulates retinogeniculate targeting independent of activity and ephrin-A signalling
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DOI：
10.1016/j.mcn.2009.04.001
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发表时间：
2009-06-22
影响因子：
3.5
通讯作者：
DiAntonio, Aaron
中科院分区：
文献类型：
--
作者：
Culican, Susan M.;Bloom, A. Joseph;DiAntonio, Aaron
哺乳动物视觉系统的正常功能需要眼睛和它们的中心目标之间的连接精确地发展。出生时。来自两只眼睛的轴突投射到背外侧膝状体核（dLGN）的宽的重叠区域。在成人中，视网膜轴突在dLGN内的定型位置分离成不同的单眼区域。这个过程是由分子线索和活动依赖性突触竞争驱动的。在这里，我们表明，Phr 1，突触形成和轴突指导的进化保守的调节器，定义了一个新的分子通路所需的适当定位的retinogeniculate预测。在视网膜中Phr 1的有条件切除后，dLGN内的眼睛特异性域受到严重干扰，尽管正常的自发视网膜波活动和单眼分离。虽然层放置显着改变，Phr 1突变体视网膜轴突在体外ephrin-A。这些研究结果表明，Phr 1是一个关键的突触前调节retinogeniculate层的位置独立的活动，隔离，或ephrin-A信号。(C)2009 Elsevier Inc. All rights reserved.
Proper functioning of the mammalian visual system requires that connections between the eyes and their central targets develop precisely. At birth. axons from the two eyes project to broad, overlapping regions of the dorsal-lateral geniculate nucleus (dLGN). In the adult, retinal axons segregate into distinct monocular regions at stereotyped locations within the dLGN. This process is driven by both molecular cues and activity-dependent synaptic competition. Here we demonstrate that Phr1, an evolutionarily conserved regulator of synapse formation and axon guidance, defines a novel molecular pathway required for proper localization of retinogeniculate projections. Following conditional excision of Phr1 in the retina, eye-specific domains within the dLGN are severely disturbed, despite normal spontaneous retinal wave activity and monocular segregation. Although layer placement is dramatically altered, Phr1 mutant retinal axons respond to ephrin-A in vitro. These findings indicate that Phr1 is a key presynaptic regulator of retinogeniculate layer placement independent of activity, segregation, or ephrin-A signaling. (C) 2009 Elsevier Inc. All rights reserved.