The Ciliary Margin Zone of the Mammalian Retina Generates Retinal Ganglion Cells.

The Ciliary Margin Zone of the Mammalian Retina Generates Retinal Ganglion Cells.
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DOI:
10.1016/j.celrep.2016.11.016
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发表时间:
2016-12-20
期刊:
影响因子:
8.8
通讯作者:
Herrera E
Herrera E
中科院分区:
生物学1区
文献类型:
--
作者:
Marcucci F;Murcia-Belmonte V;Wang Q;Coca Y;Ferreiro-Galve S;Kuwajima T;Khalid S;Ross ME;Mason C;Herrera E

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低等脊椎动物的视网膜通过整合睫状缘区(CMZ)祖细胞产生的新神经元来不断生长。哺乳动物 CMZ 是否为神经视网膜提供视网膜细胞存在争议。 CMZ 中表达 eGFP 的胚胎视网膜的实时成像显示,细胞从 CMZ 横向迁移到分化的视网膜神经节细胞 (RGC) 所在的神经视网膜。由于细胞周期调节剂 Cyclin D2 在腹侧 CMZ 中富集,我们分析了 Cyclin D2−/− 小鼠以测试 CMZ 是否是视网膜细胞的来源。 Cyclin D2 突变体中的神经发生减少,导致腹侧视网膜中的 RGC 减少。与这些发现一致,在白化视网膜中,同侧 RGC 产量的减少与 Cyclin D2+ 细胞的减少相关。总之,这些结果表明哺乳动物 CMZ 是产生 RGC 的神经源位点,其正确生成取决于 Cyclin D2 活性。
The retina of lower vertebrates grows continuously by integrating new neurons generated from progenitors in the ciliary margin zone (CMZ). Whether the mammalian CMZ provides the neural retina with retinal cells is controversial. Live-imaging of embryonic retina expressing eGFP in the CMZ shows that cells migrate laterally from the CMZ to the neural retina where differentiated retinal ganglion cells (RGCs) reside. As Cyclin D2, a cell-cycle regulator, is enriched in ventral CMZ, we analyzed Cyclin D2−/− mice to test whether the CMZ is a source of retinal cells. Neurogenesis is diminished in Cyclin D2 mutants, leading to a reduction of RGCs in the ventral retina. In line with these findings, in the albino retina, the decreased production of ipsilateral RGCs is correlated with fewer Cyclin D2+ cells. Together, these results implicate the mammalian CMZ as a neurogenic site that produces RGCs and whose proper generation depends on Cyclin D2 activity.