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DDX24 对于肌肉纤维组织的形成以及抑制创伤诱导的 Wnt 活性是必需的,而后者对于再生过程中涡虫的再生极的重建是必要的。

DDX24 is required for muscle fiber organization and the suppression of wound-induced Wnt activity necessary for pole re-establishment during planarian regeneration.

机构信息

National Centre for Biological Sciences (NCBS), Tata Institute of Fundamental Research (TIFR), Bengaluru, 560065, India; Integrative Chemical Biology (ICB), Institute for Stem Cell Science and Regenerative Medicine (inStem), Bengaluru, 560065, India.

Integrative Chemical Biology (ICB), Institute for Stem Cell Science and Regenerative Medicine (inStem), Bengaluru, 560065, India; Manipal Academy of Higher Education, Manipal, 576104, India.

出版信息

Dev Biol. 2022 Aug;488:11-29. doi: 10.1016/j.ydbio.2022.04.011. Epub 2022 May 4.

Abstract

Planarians have a remarkable ability to undergo whole-body regeneration. Successful regeneration outcome is determined by processes like polarity establishment at the wound site, which is followed by pole (organizer) specification. Interestingly, these determinants are almost exclusively expressed by muscles in these animals. However, the molecular toolkit that enables the functional versatility of planarian muscles remains poorly understood. Here we report that SMED_DDX24, a D-E-A-D Box RNA helicase, is necessary for planarian survival and regeneration. We found that DDX24 is enriched in muscles and its knockdown disrupts muscle fiber organization. This leads to defective pole specification, which in turn results in misregulation of many positional control genes specifically during regeneration. ddx24 RNAi also upregulates wound-induced Wnt signalling. Suppressing this ectopic Wnt activity rescues the knockdown phenotype by enabling better anterior pole regeneration. To summarize, our work highlights the role of an RNA helicase in muscle fiber organization, and modulating amputation-induced wnt levels, both of which seem critical for pole re-organization, thereby regulating whole-body regeneration.

摘要

涡虫具有惊人的全身再生能力。成功的再生结果取决于在伤口部位建立极性等过程,随后是极(组织者)的特化。有趣的是,这些决定因素几乎完全由这些动物的肌肉表达。然而,使涡虫肌肉具有多功能性的分子工具包仍知之甚少。在这里,我们报告了 SMED_DDX24,一种 D-E-A-D 盒 RNA 解旋酶,是涡虫生存和再生所必需的。我们发现 DDX24 在肌肉中富集,其敲低会破坏肌肉纤维组织。这导致极特化缺陷,进而导致许多位置控制基因在再生过程中特异性的失调。ddx24 RNAi 也上调了损伤诱导的 Wnt 信号。抑制这种异位 Wnt 活性通过更好地再生前极来挽救敲低表型。总之,我们的工作强调了 RNA 解旋酶在肌肉纤维组织中的作用,以及调节截肢诱导的 Wnt 水平,这两者似乎对极重组都很关键,从而调节全身再生。

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