A cell-ECM mechanism for connecting the ipsilateral eye to the brain.
A cell-ECM mechanism for connecting the ipsilateral eye to the brain.
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DOI：
10.1073/pnas.2104343118
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发表时间：
2021-10-19
影响因子：
11.1
通讯作者：
Fox MA
中科院分区：
文献类型：
--
作者：
Su J;Sabbagh U;Liang Y;Olejníková L;Dixon KG;Russell AL;Chen J;Pan YA;Triplett JW;Fox MA
视觉世界的不同特征通过解剖学上分离的电路从视网膜传递到大脑。尽管这是哺乳动物视觉通路的组织原则，但我们对引导不同类型视网膜神经元轴突进入大脑区域分离层的信号机制缺乏了解。我们通过识别来自同侧视网膜的轴突如何支配上丘的特定层来探索这个问题。我们的研究揭示了一种独特的细胞-细胞外基质识别机制，该机制指定了这些轴突到上丘的精确靶向。这种机制的缺失不仅会导致眼睛特有视觉回路的缺失，还会导致先天掠夺性视觉行为的损害。视觉世界的特征信息由视网膜中的电路解析，然后通过不同亚型的视网膜神经节细胞（RGCs）传递到大脑。来自RGC亚型的轴突在视网膜受体脑核（如上丘（SC））中分层，以提供平行和特定特征的视觉流的分离中继。在这里，我们试图确定指导这些轴突的定型层流靶向的分子机制。我们重点研究了轴突靶向深SC层下的同侧突出RGCs亚型（ipsiRGCs）。我们鉴定出一种细胞外糖蛋白Nephronectin (NPNT)，其表达仅限于ipsirgc靶向的膜下。SC衍生的NPNT和ipsiRGC表达的整合素受体都需要将ipsiRGC轴突靶向到SC的深膜下。因此，细胞-细胞外基质（ECM）识别机制指定了ipsiRGC轴突的精确层状靶向和眼睛特异性平行视觉通路的组装。
Distinct features of the visual world are transmitted from the retina to the brain through anatomically segregated circuits. Despite this being an organizing principle of visual pathways in mammals, we lack an understanding of the signaling mechanisms guiding axons of different types of retinal neurons into segregated layers of brain regions. We explore this question by identifying how axons from the ipsilateral retina innervate a specific lamina of the superior colliculus. Our studies reveal a unique cell–extracellular matrix recognition mechanism that specifies precise targeting of these axons to the superior colliculus. Loss of this mechanism not only resulted in the absence of this eye-specific visual circuit, but it led to an impairment of innate predatory visual behavior as well. Information about features in the visual world is parsed by circuits in the retina and is then transmitted to the brain by distinct subtypes of retinal ganglion cells (RGCs). Axons from RGC subtypes are stratified in retinorecipient brain nuclei, such as the superior colliculus (SC), to provide a segregated relay of parallel and feature-specific visual streams. Here, we sought to identify the molecular mechanisms that direct the stereotyped laminar targeting of these axons. We focused on ipsilateral-projecting subtypes of RGCs (ipsiRGCs) whose axons target a deep SC sublamina. We identified an extracellular glycoprotein, Nephronectin (NPNT), whose expression is restricted to this ipsiRGC-targeted sublamina. SC-derived NPNT and integrin receptors expressed by ipsiRGCs are both required for the targeting of ipsiRGC axons to the deep sublamina of SC. Thus, a cell–extracellular matrix (ECM) recognition mechanism specifies precise laminar targeting of ipsiRGC axons and the assembly of eye-specific parallel visual pathways.
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影响因子：
3.5
作者：
Ito S;Feldheim DA
通讯作者：
Feldheim DA
影响因子：
3.7
作者：
Dharmaratne N;Glendining KA;Young TR;Tran H;Sawatari A;Leamey CA
通讯作者：
Leamey CA
影响因子：
16.2
作者：
Dulabon, L;Olson, EC;Anton, ES
通讯作者：
Anton, ES
影响因子：
16.2
作者：
Di Donato, Vincenzo;De Santis, Flavia;Del Bene, Filippo
通讯作者：
Del Bene, Filippo
DOI：
10.1126/science.1176009
发表时间：
2009-11-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hynes RO
通讯作者：
Hynes RO