Mosaic deletion of Rb arrests rod differentiation and stimulates ectopic synaptogenesis in the mouse retina
Mosaic deletion of Rb arrests rod differentiation and stimulates ectopic synaptogenesis in the mouse retina
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DOI：
10.1002/cne.21059
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发表时间：
2006-09-01
影响因子：
2.5
通讯作者：
Dyer, Michael A.
中科院分区：
文献类型：
--
作者：
Johnson, Dianna A.;Donovan, Stacy L.;Dyer, Michael A.
视网膜母细胞瘤基因（Rb）调控神经祖细胞的增殖和细胞命运的分化。对于发育中的小鼠视网膜，Rb有两种不同的功能：调节视网膜祖细胞增殖和杆状光感受器的发育。正常情况下会变成杆状细胞的细胞不能成熟，在成体的细胞核外层仍然是未成熟的细胞。通过使用Chx10-Cre；RbLox/-小鼠，我们产生了一个嵌合视网膜，具有野生型和rb缺乏组织的顶基相间条纹。这提供了一种独特的模型，用于研究缺乏分化杆的区域内外丛状层的突触发生。在杆状细胞分化失败的区域，外丛状层（OPL）被破坏。水平细胞形成，体细胞排列适当，但神经突不向外侧突出。相反，许多水平细胞神经突向顶端延伸，形成异位突触，与外核层各级的光感受器相连。这些异位的光感受器末端包含突触带、具有突触囊泡的水平细胞突和具有棒状小球体特征的单个线粒体。缺乏rb的双极细胞正常分化，树突延伸至OPL，并形成与邻近野生型细胞难以区分的突触。与opl定位的突触相比，异位突触不包含双极树突。这一发现表明，水平细胞和光感受器可以形成稳定的突触，在正常的OPL边界之外缺乏双极树突。最后，对P4、P7、P12和P15视网膜的分析表明，顶端水平细胞突起是由于它们在发育过程中未能建立正常的横向突起造成的。
The retinoblastoma gene (Rb) regulates neural progenitor cell proliferation and cell fate specification and differentiation. For the developing mouse retina, two distinct functions of Rb have been described: regulation of retinal progenitor cell proliferation and rod photoreceptor development. Cells that would normally become rods fail to mature and remain as immature cells in the outer nuclear layer in the adult. By using Chx10-Cre;RbLox/- mice, we generated a chimeric retina with alternating apical-basal stripes of wild-type and Rb-deficient tissue. This provides a unique model with which to study synaptogenesis at the outer plexiform layer within regions that lack differentiated rods. In regions where rods failed to differentiate, the outer plexiform layer (OPL) was disrupted. Horizontal cells formed, and their somata were appropriately aligned, but their neurites did not project laterally. Instead many horizonal cell neurites extended apically, forming ectopic synapses with photoreceptors at all levels of the outer nuclear layer. These ectopic photoreceptor terminals contained synaptic ribbons, horizontal cell processes with synaptic vesicles, and a single mitochrondrion characteristic of rod spherules. Rb-deficient bipolar cells differentiated normally, extended dendrites to the OPL, and formed synapses that were indistinguishable from adjacent wild-type cells. In contrast to OPL-positioned synapses, ectopic synapses did not contain bipolar dendrites. This finding suggests that horizontal cells and photoreceptors can form stable synapses that are devoid of bipolar dendrites outside the normal boundaries of the OPL. Finally, analysis of P4, P7, P12, and P15 retinae suggests that the apical horizontal cell processes result from their failure to establish their normal lateral projections during development.