Cell-type specific roles for PTEN in establishing a functional retinal architecture.
Cell-type specific roles for PTEN in establishing a functional retinal architecture.
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DOI：
10.1371/journal.pone.0032795
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Schuurmans C
中科院分区：
文献类型：
--
作者：
Cantrup R;Dixit R;Palmesino E;Bonfield S;Shaker T;Tachibana N;Zinyk D;Dalesman S;Yamakawa K;Stell WK;Wong RO;Reese BE;Kania A;Sauvé Y;Schuurmans C
视网膜具有独特的三维结构，其精确的组织允许对视野进行完整的采样。沿着径向或顶基底轴，视网膜神经元及其树突和轴突乔木被分离成层，而垂直于该轴，在切向平面中，六种神经元类型中的四种形成图案化的细胞阵列或马赛克。目前，控制视网膜细胞定位的分子线索还没有得到很好的理解，特别是那些在切平面中操作的分子线索。在这里，我们研究了PTEN磷酸酶在建立功能性视网膜结构中的作用。在发育中的视网膜中，PTEN优先定位于神经节细胞、无长突细胞和水平细胞，其胞体在切平面上呈马赛克状分布。产生视网膜特异性Pten基因敲除导致视网膜神经节，无长突和水平细胞肥大，和扩大的内部网状层。Pten突变体嵌合体群体的间距也异常，因为他们的过程中的树枝状和束状图案，显示细胞类型的径向和切向尺寸的特定缺陷。在Pten突变体视网膜电图中也观察到不规则的振荡电位，表明异步无长突细胞放电。此外，虽然Pten突变体RGC轴突靶向适当的大脑区域，但Pten突变体动物的视动空间敏锐度降低。最后，虽然Pten突变体视网膜的一些特征似乎与Dscam突变小鼠中报道的那些相似，但在没有Dscam的情况下，PTEN表达和活性是正常的。我们的结论是，Pten调节染色体定位和神经突分枝模式的视网膜细胞的一个子集，形成马赛克，可能独立运作的Dscam，至少在胚胎期。因此，我们的研究结果揭示了一个意想不到的水平的多用途磷酸酶的细胞特异性，并确定Pten作为一种新的细胞定位途径在视网膜中的组成部分。
The retina has a unique three-dimensional architecture, the precise organization of which allows for complete sampling of the visual field. Along the radial or apicobasal axis, retinal neurons and their dendritic and axonal arbors are segregated into layers, while perpendicular to this axis, in the tangential plane, four of the six neuronal types form patterned cellular arrays, or mosaics. Currently, the molecular cues that control retinal cell positioning are not well-understood, especially those that operate in the tangential plane. Here we investigated the role of the PTEN phosphatase in establishing a functional retinal architecture. In the developing retina, PTEN was localized preferentially to ganglion, amacrine and horizontal cells, whose somata are distributed in mosaic patterns in the tangential plane. Generation of a retina-specific Pten knock-out resulted in retinal ganglion, amacrine and horizontal cell hypertrophy, and expansion of the inner plexiform layer. The spacing of Pten mutant mosaic populations was also aberrant, as were the arborization and fasciculation patterns of their processes, displaying cell type-specific defects in the radial and tangential dimensions. Irregular oscillatory potentials were also observed in Pten mutant electroretinograms, indicative of asynchronous amacrine cell firing. Furthermore, while Pten mutant RGC axons targeted appropriate brain regions, optokinetic spatial acuity was reduced in Pten mutant animals. Finally, while some features of the Pten mutant retina appeared similar to those reported in Dscam-mutant mice, PTEN expression and activity were normal in the absence of Dscam. We conclude that Pten regulates somal positioning and neurite arborization patterns of a subset of retinal cells that form mosaics, likely functioning independently of Dscam, at least during the embryonic period. Our findings thus reveal an unexpected level of cellular specificity for the multi-purpose phosphatase, and identify Pten as an integral component of a novel cell positioning pathway in the retina.
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DOI：
10.1002/cne.22270
发表时间：
2010-04-15
期刊：
The Journal of comparative neurology
影响因子：
--
作者：
Keeley PW;Reese BE
通讯作者：
Reese BE
影响因子：
16.2
作者：
Fuerst, Peter G.;Bruce, Freyja;Tian, Miao;Wei, Wei;Elstrott, Justin;Feller, Maria B.;Erskine, Lynda;Singer, Joshua H.;Burgess, Robert W.
通讯作者：
Burgess, Robert W.
影响因子：
5.3
作者：
Basile, JR;Afkhami, T;Gutkind, JS
通讯作者：
Gutkind, JS
影响因子：
3.3
作者：
Fraser, M. M.;Bayazitov, I. T.;Baker, S. J.
通讯作者：
Baker, S. J.
影响因子：
2.5
作者：
Alam, S;Zinyk, D;Schuurmans, C
通讯作者：
Schuurmans, C