The role of miR-124a in early development of the Xenopus eye.
The role of miR-124a in early development of the Xenopus eye.
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miR-124a 在非洲爪蟾眼睛早期发育中的作用
DOI：
10.1016/j.mod.2009.08.002
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发表时间：
2009-10
影响因子：
2.6
通讯作者：
He, Rongqiao
中科院分区：
文献类型：
--
作者：
Qiu, Rong;Liu, Kaili;Liu, Ying;Mo, Weichuan;Flynt, Alex S.;Patton, James G.;Kar, Amar;Wu, Jane Y.;He, Rongqiao
据报道，miR-124 a在包括眼睛在内的中枢神经系统中丰富，并且与几个物种的神经发生有关。然而，miR-124 a在眼睛中的作用仍不清楚。在这项研究中，我们发现，miR-124 a在非洲爪蟾开始沿着神经褶皱，包括突出的眼睛原基，在低水平在18阶段左右，其表达水平逐渐增加，在神经管和眼睛胚胎发育到后期阶段，然后保持在高水平的眼睛到成年阶段。在8细胞阶段显微注射miR-124 a前体导致视神经和视杯畸形，表明在早期胚胎发育期间维持低水平miR-124 a的重要性。此外，miR-124 a过表达显著下调其预测的靶点Lhx 2、Hairy 2、Gli 3、NeuroD 1和Otx 2在眼原基中/周围的表达，并且miR-124 a与Lhx 2的3′ UTR的相互作用抑制基因表达，如荧光素酶测定所示。此外，过量的miR-124 a抑制视网膜发生期间爪蟾胚胎眼中的细胞增殖。这些结果表明，miR-124 a在控制眼睛形态发生和神经发生的遗传网络中充当转录后调节因子。miR-124 a与遗传网络的早期相互作用的机制也可能在其成熟和成年眼睛和大脑中的后期作用中持续存在。
It has been reported that miR-124a is abundant in the central nervous system including the eye, and is related to neurogenesis in several species. However, the role of miR-124a in the eye remains unclear. In this study, we show that the expression of miR-124a in Xenopus laevis begins along the neural fold, including the protruding eye anlagen, at a low level at around stage 18; its expression level gradually increases in the neural tube and the eye as embryos develop into later stages and then maintains at a high level in eye to adult stages. Microinjection of a miR-124a precursor at the 8-cell stage leads to malformation of the optic nerve and optic cup, indicating the importance of maintaining low levels of miR-124a during early embryonic development. In addition, miR-124a overexpression markedly down regulates the expression of its predicted targets Lhx2, Hairy2, Gli3, NeuroD1 and Otx2 in/around the eye anlagen, and the interaction of miR-124a with the 3′ UTR of Lhx2 represses gene expression as shown by luciferase assays. Moreover, excess miR-124a inhibits cell proliferation in the eye of Xenopus embryos during retinogenesis. These results indicate that miR-124a acts as a post-transcriptional regulator in the genetic network controlling eye morphogenesis and neurogenesis. The mechanism of miR-124a’s early interaction with the genetic network may also persist in its later role in the maturing and adult eye and brain.
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