miR-205 is a critical regulator of lacrimal gland development.
miR-205 is a critical regulator of lacrimal gland development.
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DOI：
10.1016/j.ydbio.2017.05.012
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发表时间：
2017-07-01
影响因子：
2.7
通讯作者：
McManus, Michael T.
中科院分区：
文献类型：
--
作者：
Farmer, D'Juan T.;Finley, Jennifer K.;Chen, Feeling Y.;Tarifeno-Saldivia, Estefania;McNamara, Nancy A.;Knox, Sarah M.;McManus, Michael T.
泪膜保护陆生动物的眼表，泪腺提供维持其生存所必需的重要的含水分泌物。尽管泪腺在眼睛健康中很重要，但其发育的分子方面仍然知之甚少。我们发现一个非编码的RNA(miR-205)是泪腺发育的重要基因。缺乏miR-205的小鼠无法正常发育泪腺，将这种非编码RNA确立为泪腺发育的关键调节因子。具体地说，超过一半的被敲除的泪腺从未启动，这表明miR-205在泪腺发育的早期阶段发挥着关键作用。RNA-seq分析发现了几个上调的miR-205靶点，它们可能会干扰信号以削弱泪腺的启动。支持这一数据的是，小鼠泪腺启动的驱动力Fgf10和miR-205的组合上位性缺失加剧了泪腺的表型。我们开发了一个分子变阻器模型，其中miR-205调节与Fgf10相关的信号通路，以调节腺的发育。这些数据表明，单个microRNA是小鼠早期泪腺发育的关键调节因子，并突出了microRNA在器官发生中的重要作用。这项研究确定了miR-205在胚胎器官发生，特别是泪腺发育中的作用。
The tear film protects the terrestrial animal’s ocular surface and the lacrimal gland provides important aqueous secretions necessary for its maintenance. Despite the importance of the lacrimal gland in ocular health, molecular aspects of its development remain poorly understood. We have identified a noncoding RNA (miR-205) as an important gene for lacrimal gland development. Mice lacking miR-205 fail to properly develop lacrimal glands, establishing this noncoding RNA as a key regulator of lacrimal gland development. Specifically, more than half of knockout lacrimal glands never initiated, suggesting a critical role of miR-205 at the earliest stages of lacrimal gland development. RNA-seq analysis uncovered several up-regulated miR-205 targets that may interfere with signaling to impair lacrimal gland initiation. Supporting this data, combinatorial epistatic deletion of Fgf10, the driver of lacrimal gland initiation, and miR-205 in mice exacerbates the lacrimal gland phenotype. We develop a molecular rheostat model where miR-205 modulates signaling pathways related to Fgf10 in order to regulate glandular development. These data show that a single microRNA is a key regulator for early lacrimal gland development in mice and highlights the important role of microRNAs during organogenesis. This study establishes a role of miR-205 during embryonic organogenesis, and specifically lacrimal gland development.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
3.7
作者：
Dorà NJ;Collinson JM;Hill RE;West JD
通讯作者：
West JD
影响因子：
4.6
作者：
Dean, C;Ito, M;Lang, RA
通讯作者：
Lang, RA
影响因子：
4.8
作者：
Kawano, Satoshi;Ikeda, Wataru;Takai, Yoshimi
通讯作者：
Takai, Yoshimi
影响因子：
2.7
作者：
Hayashi, Toru;Koyama, Noriko;Kashimata, Masanori
通讯作者：
Kashimata, Masanori