Post-transcriptional mechanisms contribute to Etv2 repression during vascular development.
Post-transcriptional mechanisms contribute to Etv2 repression during vascular development.
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DOI：
10.1016/j.ydbio.2013.08.028
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发表时间：
2013-12-01
影响因子：
2.7
通讯作者：
Lawson, Nathan D.
中科院分区：
文献类型：
--
作者：
Moore, John C.;Sheppard-Tindell, Sarah;Shestopalov, Ilya A.;Yamazoe, Sayumi;Chen, James K.;Lawson, Nathan D.
etv2是内皮特异性ETS转录因子，对脊椎动物血管分化和形态发生至关重要。虽然最近的数据表明，在血管发育过程中，Etv2是动态调节的，但对这一过程的机制知之甚少。在这里，我们发现etv2转录和蛋白表达在斑马鱼血管发育过程中是高度动态的，在早期体细胞发生时明显，随后随着发育的进行而下调。在斑马鱼胚胎中，在躯体发育中期之前（而不是之后）诱导敲低Etv2会导致严重的血管缺陷，这表明在外侧中胚层向内皮细胞谱系的早期承诺中具有特定作用。因此，在嵌合胚胎中，过表达etv2的细胞表现出增强的内皮细胞系的能力。我们进一步发现etv2 3 '非翻译区（UTR）能够抑制内皮自主转基因，并包含let-7 microrna家族成员的结合位点。在传感器检测中，let-7a的异位表达可以抑制etv2 3'UTR，也能够阻断内源性etv2蛋白的表达，导致内皮基因的减少。最后，我们观察到Etv2蛋白水平在母系合子dicer1突变胚胎中持续存在，这表明在血管发育过程中，microrna有助于抑制其表达。综上所述，我们的研究结果表明，etv2在早期发育过程中起作用，指定内皮细胞谱系，然后部分通过microrna的转录后抑制而下调，从而允许正常的血管发育。
etv2 is an endothelial-specific ETS transcription factor that is essential for vascular differentiation and morphogenesis in vertebrates. While recent data suggest that Etv2 is dynamically regulated during vascular development, little is known about the mechanisms involved in this process. Here, we find that etv2 transcript and protein expression are highly dynamic during zebrafish vascular development, with both apparent during early somitogenesis and subsequently down-regulated as development proceeds. Inducible knockdown of Etv2 in zebrafish embryos prior to mid-somitogenesis stages, but not later, caused severe vascular defects, suggesting a specific role in early commitment of lateral mesoderm to the endothelial linage. Accordingly, Etv2-overexpressing cells showed an enhanced ability to commit to endothelial lineages in mosaic embryos. We further find that the etv2 3’ untranslated region (UTR) is capable of repressing an endothelial autonomous transgene and contains binding sites for members of the let-7 family of microRNAs. Ectopic expression of let-7a could repress the etv2 3’UTR in sensor assays and was also able to block endogenous Etv2 protein expression, leading to concomitant reduction of endothelial genes. Finally, we observed that Etv2 protein levels persisted in maternal-zygotic dicer1 mutant embryos, suggesting that microRNAs contribute to its repression during vascular development. Taken together, our results suggest that etv2 acts during early development to specify endothelial lineages and is then down-regulated, in part through post-transcriptional repression by microRNAs, to allow normal vascular development.
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影响因子：
2.4
作者：
Hauptmann, G
通讯作者：
Hauptmann, G
影响因子：
64.5
作者：
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影响因子：
3.7
作者：
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通讯作者：
Lin S
影响因子：
4.8
作者：
Iljin, K;Dube, A;Alitalo, K
通讯作者：
Alitalo, K