Neuronal clustering and fasciculation phenotype in Dscam- and Bax-deficient mouse retinas.

Neuronal clustering and fasciculation phenotype in Dscam- and Bax-deficient mouse retinas.
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DOI:
10.1002/cne.23033
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发表时间:
2012-05-01
影响因子:
2.5
通讯作者:
Reese, Benjamin E.
Reese, Benjamin E.
中科院分区:
医学3区
文献类型:
--
作者:
Keeley, Patrick W.;Sliff, Buranee J.;Lee, Sammy C. S.;Fuerst, Peter G.;Burgess, Robert W.;Eglen, Stephen J.;Reese, Benjamin E.

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单个类型的视网膜神经元分布成最小化与相邻细胞的接近度。这些相同的细胞类型中的许多延伸树突以提供视网膜表面的覆盖。对于某些细胞类型,在缺乏唐氏综合征细胞粘附分子Dscam的小鼠中,视网膜镶嵌的这两个基本特征被破坏,表现出异常的胞体聚集和树突成束。Dscam突变小鼠视网膜也表现出这些相同细胞类型的过量。本研究比较了Dscam突变型视网膜与β-敲除型视网膜的这两个特征,其中也存在过量的两种细胞类型,即黑视素阳性视网膜神经节细胞(MRGCs)和多巴胺能无长突细胞(DAC)。对两个群体的整个视网膜进行免疫标记,并对每个标记的索马作图。对于MRGCs,我们发现了Dscam的基因剂量效应,Dscam+/-视网膜显示出细胞数量、聚集和成束的较小增加。奇怪的是,Bax-/-视网膜,显示MRGCs的数量在Dscam-/-与Dscam+/-视网膜中发现的中间,也具有聚类和成束表型,这些表型在具有这些基因型的视网膜中间。相比之下,DAC显示Dscam-/-和Bax-/-视网膜的变化与DAC数量的增加无关。尽管只有适度的聚集,但Dscam-/-视网膜中的肌束震颤表型尤其突出。这些结果表明,在Dscam突变体视网膜中观察到的染色体簇集和成束不是Dscam缺陷所独有的,并且通过不同的视网膜细胞类型而独特地表现出来。
Individual types of retinal neurons are distributed to minimize proximity to neighboring cells. Many of these same cell types extend dendrites to provide coverage of the retinal surface. These two cardinal features of retinal mosaics are disrupted, for certain cell types, in mice deficient for the Down syndrome cell adhesion molecule, Dscam, exhibiting an aberrant clustering of somata and fasciculation of dendrites. The Dscam-mutant mouse retina also exhibits excess numbers of these same cell types. The present study compared these two features in Dscam-mutant retinas with the Bax-knockout retina, in which excess numbers of two of these cell types, the melanopsin-positive retinal ganglion cells (MRGCs) and the dopaminergic amacrine cells (DACs), are also present. Whole retinas were immunolabeled for both populations, and every labeled soma was plotted. For the MRGCs, we found a gene dosage effect for Dscam, with the Dscam+/- retinas showing smaller increases in cell number, clustering and fasciculation. Curiously, Bax-/- retinas, showing numbers of MRGCs intermediate to those found in the Dscam-/- versus Dscam+/- retinas, also had clustering and fasciculation phenotypes that were intermediate to retinas with those genotypes. DACs, by comparison, showed changes in both the Dscam-/- and Bax-/- retinas that did not correlate with their increases in DAC number. The fasciculation phenotype in the Dscam-/- retina was particularly prominent despite only modest clustering. These results demonstrate that the somal clustering and fasciculation observed in the Dscam-mutant retina are not unique to Dscam-deficiency, and are manifested distinctively by different retinal cell-types.
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期刊: The Journal of comparative neurology
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发表时间: 2009-04-01
期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
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