Dicer is required for the transition from early to late progenitor state in the developing mouse retina.
Dicer is required for the transition from early to late progenitor state in the developing mouse retina.
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DOI：
10.1523/jneurosci.4982-09.2010
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发表时间：
2010-03-17
期刊：
影响因子：
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通讯作者：
Reh TA
中科院分区：
文献类型：
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作者：
Georgi SA;Reh TA
microRNAs（miRNAs）是一类19-25个核苷酸的小分子RNAs，通过转录后调节mRNA的翻译和降解来影响基因的表达，近年来已成为神经发育的重要调控因子。使用条件敲除Dicer，一种miRNA成熟所需的RNase III酶，以前的研究已经证明了miRNA在小鼠皮质，内耳和嗅觉发育中的重要作用。然而，之前的一项研究使用Chx 10 cre小鼠删除视网膜祖细胞中的Dicer，报告在出生后第二周之前视网膜没有缺陷，这表明miRNAs不是小鼠视网膜发育所必需的。为了进一步研究miRNAs在视网膜发育过程中的作用并解决这一明显的冲突，我们使用不同的（α Pax 6cre）转基因小鼠系有条件地敲除Dicer。与以前的研究相比，我们证明了miRNAs在小鼠视网膜发育过程中的重要作用。在胚胎视网膜中没有Dicer的情况下，早期产生的细胞类型-神经节细胞和水平细胞-的产生增加，并且晚期祖细胞的标记物不表达。这种表型持续到出生后的视网膜，在那里我们发现Dicer缺陷的祖细胞不能产生晚出生的细胞类型，如杆和Müller胶质细胞，但继续产生神经节细胞。我们进一步表征了视网膜祖细胞分化过程中miRNA的动态表达，并提供了视网膜发育过程中表达的miRNA的全面概况。我们的结论是，Dicer是必要的视网膜祖细胞的能力的发育变化。
MicroRNAs (miRNAs), small 19-25 nucleotide RNAs that influence gene expression through post-transcriptional regulation of mRNA translation and degradation, have recently emerged as important regulators of neural development. Using conditional knockout of Dicer, an RNase III enzyme required for miRNA maturation, previous studies have demonstrated an essential role for miRNAs in mouse cortical, inner ear, and olfactory development. However, a previous study using a Chx10cre mouse to delete Dicer in retinal progenitors reported no defects in the retina before the second postnatal week, suggesting that miRNAs are not required for mouse retinal development. In an effort to further study the role of miRNAs during retinal development and resolve this apparent conflict, we conditionally knocked-out Dicer using a different (αPax6cre) line of transgenic mice. In contrast to the previous study, we demonstrate an essential role for miRNAs during mouse retinal development. In the absence of Dicer in the embryonic retina, production of early generated cell types- ganglion and horizontal cells- is increased, and markers of late progenitors are not expressed. This phenotype persists into postnatal retina, where we find the Dicer-deficient progenitors fail to generate late-born cell types like rods and Müller glia, but continue to generate ganglion cells. We further characterize the dynamic expression of miRNAs during retinal progenitor differentiation, and provide a comprehensive profile of miRNAs expressed during retinal development. We conclude that Dicer is necessary for the developmental change in competence of the retinal progenitor cells.