miR-196 is an essential early-stage regulator of tail regeneration, upstream of key spinal cord patterning events
miR-196 is an essential early-stage regulator of tail regeneration, upstream of key spinal cord patterning events
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DOI：
10.1016/j.ydbio.2009.08.008
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发表时间：
2009-10-15
影响因子：
2.7
通讯作者：
Echeverri, Karen
中科院分区：
文献类型：
--
作者：
Sehm, Tina;Sachse, Christoph;Echeverri, Karen
蝾螈有非凡的能力，再生许多身体部位后，灾难性的伤害，包括一个功能齐全的脊髓后，尾巴截肢。这个过程是如何如此精细地受到良好调节的分子基础，确保每次都能忠实地复制缺失的结构，仍然知之甚少。因此，进行了蝾螈（Ambystoma mexicanum）再生期间microRNA表达和功能的研究。使用基于微阵列的分析，发现与成熟组织相比，78种高度保守的microRNA在尾部再生的早期阶段显示出表达水平的显著变化。然后进一步分析在早期尾胚基和脊髓中高度上调的miR-196的作用。在这种情况下，抑制miR-196表达导致再生缺陷，产生异常缩短的尾，脊髓末端囊泡形成缺陷。对这种表型的更详细表征揭示了miR-196通路的下游组分，包括脊髓内组织模式的关键效应物/调节物，包括BMP 4和Pax 7。因此，我们的数据集将miR-196确定为尾部再生的重要调节因子，作用于脊髓内基于关键BMP 4和Pax 7的图案化事件的上游。(C)2009 Elsevier Inc. All rights reserved.
Salamanders have the remarkable ability to regenerate many body parts following catastrophic injuries, including a fully functional spinal cord following a tail amputation. The molecular basis for how this process is so exquisitely well-regulated, assuring a faithful replication of missing structures every time, remains poorly understood. Therefore a study of microRNA expression and function during regeneration in the axolotl, Ambystoma mexicanum, was undertaken. Using microarray-based profiling, it was found that 78 highly conserved microRNAs display significant changes in expression levels during the early stages of tail regeneration, as compared to mature tissue. The role of miR-196, which was highly upregulated in the early tail blastema and spinal cord, was then further analyzed. Inhibition of miR-196 expression in this context resulted in a defect in regeneration, yielding abnormally shortened tails with spinal cord defects in formation of the terminal vesicle. A more detailed characterization of this phenotype revealed downstream components of the miR-196 pathway to include key effectors/regulators of tissue patterning within the spinal cord, including BMP4 and Pax7. As such, our dataset establishes miR-196 as an essential regulator of tail regeneration, acting upstream of key BMP4 and Pax7-based patterning events within the spinal cord. (C) 2009 Elsevier Inc. All rights reserved.