Different classes of small RNAs are essential for head regeneration in the planarian Dugesia japonica
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RESEARCH ARTICLE
Open Access
Different classes of small RNAs are essential for head regeneration in the planarian Dugesia japonica Zhonghong Cao1*† , David Rosenkranz2†, Suge Wu1†, Hongjin Liu1, Qiuxiang Pang1, Xiufang Zhang1, Baohua Liu1* and Bosheng Zhao1*
Abstract Background: Planarians reliably regenerate all body parts after injury, including a fully functional head and central nervous system. But until now, the expression dynamics and functional role of miRNAs and other small RNAs during the process of head regeneration are not well understood. Furthermore, little is known about the evolutionary conservation of the relevant small RNAs pathways, rendering it difficult to assess whether insights from planarians will apply to other taxa. Results: In this study, we applied high throughput sequencing to identify miRNAs, tRNA fragments and piRNAs that are dynamically expressed during head regeneration in Dugesia japonica. We further show that knockdown of selected small RNAs, including three novel Dugesia-specific miRNAs, during head regeneration induces severe defects including abnormally small-sized eyes, cyclopia and complete absence of eyes. Conclusions: Our findings suggest that a complex pool of small RNAs takes part in the process of head regeneration in Dugesia japonica and provide novel insights into global small RNA expression profiles and expression changes in response to head amputation. Our study reveals the evolutionary conserved role of miR-124 and brings further promising candidate small RNAs into play that might unveil new avenues for inducing restorative programs in nonregenerative organisms via small RNA mimics based therapies. Keywords: Dugesia japonica, Head regeneration, Micro RNAs, Piwi-interacting RNAs, tRNA fragments, miR-124
Background The limited regenerative capabilities of most vertebrates including humans, particularly regarding damage to the central nervous system (CNS), call for effective therapies that foster the replacement or healing of wounded tissues. Therefore it is imperative to understand the molecular mechanisms of
* Correspondence: [email protected]; [email protected]; [email protected] † Zhonghong Cao, David Rosenkranz and Suge Wu contributed equally to this work. 1 School of Life Sciences, Shandong University of Technology, 266 Xincun Western Road, Zibo 255049, People’s Republic of China Full list of author information is available at the end of the article
regeneration and signal networks that induce and promote this complex process. Planarian flatworms possess an extensive potential of regeneration and are one of the few animal species that can easily regenerate their head after decapitation including the complete neoformation of a functional brain within 7 days [1–4]. Despite their relatively simple morphology, planarians have a highly structured CNS featuring a true brain consisting of a large number of different neuronal cell types [5, 6], a well-defined adult stem cell population comprising roughly 30% of all CNS cells and a clear anterior-posterior (A/P
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