MEGF10 and MEGF11 mediate homotypic interactions required for mosaic spacing of retinal neurons.

MEGF10 and MEGF11 mediate homotypic interactions required for mosaic spacing of retinal neurons.
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DOI:
10.1038/nature10877
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发表时间:
2012-03-11
期刊:
影响因子:
64.8
通讯作者:
Sanes, Joshua R.
Sanes, Joshua R.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kay, Jeremy N.;Chu, Monica W.;Sanes, Joshua R.

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在神经系统的许多部位,神经元体状体显示出有序的空间排列。在视网膜中,许多单个亚型的神经元形成了称为嵌合体的规则阵列:与偶然发生的情况相比,它们与同一亚型的近邻的可能性较小,从而导致了将它们分开的“排除区”。马赛克排列提供了一种机制,将每种细胞类型均匀地分布在视网膜上,确保视野的所有部分都可以接触到一整套处理元素。值得注意的是,嵌合体是相互独立的:虽然一个亚型的神经元不太可能与另一个亚型相同的神经元相邻,但它与其他亚型相邻神经元的空间关系没有限制。这种独立性导致了一种假设,即由特定亚型表达的分子线索通过调节同型(亚型内)短程排斥相互作用而形成镶嵌图案。然而,到目前为止,还没有发现显示这种活性的分子,所以这一假说仍然没有得到验证。在这里,我们证明了两个相关的跨膜蛋白,MEGF10和MEGF11,在两种视网膜中间神经元亚型--星状爆发型无长突细胞(SACS)和水平细胞(HCS)--形成嵌合体的过程中发挥了关键作用。到目前为止,MEGF10/11及其无脊椎动物近亲秀丽线虫CED-1和果蝇Draper主要被研究为在细胞凋亡或轴突损伤后吞噬碎片所必需的受体。我们的结果表明,这个基因家族的成员也可以作为亚型特异的配基来形成神经元阵列。
In many parts of the nervous system, neuronal somata display orderly spatial arrangements. In the retina, neurons of numerous individual subtypes form regular arrays called mosaics: they are less likely to be near neighbors of the same subtype than would occur by chance, resulting in “exclusion zones” that separate them. Mosaic arrangements provide a mechanism to distribute each cell type evenly across the retina, ensuring that all parts of the visual field have access to a full set of processing elements. Remarkably, mosaics are independent of each other: while a neuron of one subtype is unlikely to be adjacent to another of the same subtype, there is no restriction on its spatial relationship to neighboring neurons of other subtypes. This independence has led to the hypothesis that molecular cues expressed by specific subtypes pattern mosaics by mediating homotypic (within-subtype) short-range repulsive interactions. To date, however, no molecules have been identified that show such activity, so this hypothesis remains untested. Here, we demonstrate that two related transmembrane proteins, MEGF10 and MEGF11, play critical roles in formation of mosaics by two retinal interneuron subtypes, starburst amacrine cells (SACs) and horizontal cells (HCs). MEGF10/11 and their invertebrate relatives C. elegans CED-1 and Drosophila Draper, have hitherto been studied primarily as receptors necessary for engulfment of debris following apoptosis or axonal injury. Our results demonstrate that members of this gene family can also serve as subtype-specific ligands that pattern neuronal arrays.
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