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首页> 外文期刊>Nature >Transmembrane semaphorin signalling controls laminar stratification in the mammalian retina
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Transmembrane semaphorin signalling controls laminar stratification in the mammalian retina

机译：跨膜semaphorin信号控制哺乳动物视网膜中的层状分层

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摘要

In the vertebrate retina, establishment of precise synaptic connections among distinct retinal neuron cell types is critical for processing visual information and for accurate visual perception. Retinal ganglion cells (RGCs), amacrine cells and bipolar cells establish stereotypic neurite arborization patterns to form functional neural circuits in the inner plexiform layer (IPL),a laminar region that is conventionally divided into five major parallel sublaminae. However, the molecular mechanisms governing distinct retinal subtype targeting to specific sublaminae within the IPL remain to be elucidated. Here we show that the transmembrane semaphorin Sema6A signals through its receptor PlexinA4 (PlexA4) to control lamina-specific neuronal stratification in the mouse retina. Expression analyses demonstrate that Sema6A and PlexA4 proteins are expressed in a complementary fashion in the developing retina: Sema6A in most ON sublaminae and PlexA4 in OFF sublaminae of the IPL. Mice with null mutations in PlexA4 or Sema6A exhibit severe defects in stereotypic lamina-specific neurite arborization of tyrosine hydroxylase (TH)-expressing dopaminergic amacrine cells, intrinsically photosensitive RGCs (ipRGCs) and calbindin-positive cells in the IPL. Sema6A and PlexA4 genetically interact in vivo for the regulation of dopaminergic amacrine cell laminar targeting. Therefore, neuronal targeting to subdivisions of the IPL in the mammalian retina is directed by repulsive transmembrane guidance cues present on neuronal processes.
机译：在脊椎动物的视网膜中，在不同的视网膜神经元细胞类型之间建立精确的突触连接对于处理视觉信息和准确的视觉感知至关重要。视网膜神经节细胞（RGCs），无长突细胞和双极细胞建立定型的神经突乔化模式，以在内部丛状层（IPL）中形成功能性神经回路，该层状区域通常分为五个主要的平行亚层。然而，仍需要阐明控制IPL内特定亚膜层的不同视网膜亚型的分子机制。在这里，我们显示跨膜信号量Sema6A信号通过其受体PlexinA4（PlexA4）来控制小鼠视网膜中的层特异性神经元分层。表达分析表明，Sema6A和PlexA4蛋白在发育中的视网膜中以互补方式表达：在IPL的大多数ON子层中为Sema6A，在OFF子层中为PlexA4。在PlexA4或Sema6A中具有无效突变的小鼠在表达酪氨酸羟化酶（TH）的多巴胺能无长春碱细胞，固有光敏RGC（ipRGC）和钙结合蛋白阳性细胞中的定型椎板特异性神经突树突中显示严重缺陷。 Sema6A和PlexA4在体内遗传相互作用，以调节多巴胺能无长突细胞层流靶向。因此，在神经元过程中存在的排斥性跨膜引导提示可指导将神经元靶向哺乳动物视网膜中IPL的各个分支。

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  • 来源
    《Nature》 |2011年第7333期|p.259-263|共5页
  • 作者

    Ryota L. Matsuoka; Kim T. Nguyen-Ba-Charvet; Aijaz Parray; Tudor C. Badea; Alain Chedotal; Alex L. Kolodkin;

  • 作者单位

    The Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA,Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA;

    Institut National de la Santeetde la Recherche Medicale(INSERM),UMRS968,lnstitutdela Vision, F-75012 Paris, France,Universite PierreetMarieCurie(UPMC)ParisVI,UMRS968,lnstitutdelaVision,F-75012 Paris, France,Centre National de la Recherche Scientifique (CNRS) UMR 7210, Institut de la Vision, F-75012 Paris, France;

    Institut National de la Santeetde la Recherche Medicale(INSERM),UMRS968,lnstitutdela Vision, F-75012 Paris, France,Universite PierreetMarieCurie(UPMC)ParisVI,UMRS968,lnstitutdelaVision,F-75012 Paris, France,Centre National de la Recherche Scientifique (CNRS) UMR 7210, Institut de la Vision, F-75012 Paris, France,Retinal Circuit Development & Genetics Unit Neurobiology-Neurodegeneration and Repair Laboratory, National Eye Institute, Bethesda, Maryland 20892, USA;

    Department of Molecular Biology and Genetics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA,Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA;

    Institut National de la Santeetde la Recherche Medicale(INSERM),UMRS968,lnstitutdela Vision, F-75012 Paris, France,Universite PierreetMarieCurie(UPMC)ParisVI,UMRS968,lnstitutdelaVision,F-75012 Paris, France,Centre National de la Recherche Scientifique (CNRS) UMR 7210, Institut de la Vision, F-75012 Paris, France;

    The Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA,Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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