activin-2 is required for regeneration of polarity on the planarian anterior-posterior axis.
activin-2 is required for regeneration of polarity on the planarian anterior-posterior axis.
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激活素-2是涡虫前-后轴极性再生所必需的。
DOI：
10.1371/journal.pgen.1009466
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发表时间：
2021-03
期刊：
影响因子：
4.5
通讯作者：
Reddien PW
中科院分区：
文献类型：
--
作者：
Cloutier JK;McMann CL;Oderberg IM;Reddien PW
涡虫是扁虫，可以进行全身再生。这种能力包括一种区分需要头部再生的正面伤口和需要尾巴再生的正面伤口的机制。研究了这种正反再生极性决定是如何做出的，以确定再生中组织同一性规范的基本原则。我们报道了激活素-2的抑制，它编码激活素样信号配体，导致截肢后异位后面向头部的再生。在未受伤涡虫的组织转换过程中，位置信息在肌肉中组成性地表达以维持适当的模式。位置信息包括在后部表达的Wnt和在前部表达的Wnt拮抗剂。截肢后，几个创伤诱导的基因促进位置信息的重建。头对尾再生的决定涉及Wnt拮抗剂notn在面向前而不是面向后的伤口上的优先伤口诱导。nottum的不对称激活代表了头和尾再生之间最早已知的分子区别，但它是如何发生的尚不清楚。激活素-2 RNAi动物在前后面向伤口处显示对称的伤口诱导的淋巴结激活，为其异位头后表型提供了分子解释。激活素-2 RNAi动物也表现出前后（AP）轴分裂，在前囊胚中出现两个头，在后囊胚中出现各种头尾组合。这与前极异位成核有关，前极是头尖肌细胞，在面向后的伤口上促进AP和中外侧（ML）模式。这些发现揭示了激活素信号在确定再生特异性ap轴模式事件的结果中的作用。动物再生的一个核心问题是动物如何决定要再生的身体部位。涡虫是一种扁虫，可以再生任何缺失的身体区域，并研究确定再生机制。在横截面，一个知之甚少的机制指定再生的头或尾。这种头对尾的再生决策过程被称为再生极性，人们已经研究了一个多世纪，以确定具体的再生机制。编码Wnt拮抗剂的notum基因在受伤后数小时内被诱导，优先用于正面伤口，在那里它指定头部再生。我们报道激活素信号是再生极性所必需的，并且在面向前方和后方的伤口上潜在的不对称激活。我们认为激活素信号广泛参与动物王国的再生特异性反应。
Planarians are flatworms and can perform whole-body regeneration. This ability involves a mechanism to distinguish between anterior-facing wounds that require head regeneration and posterior-facing wounds that require tail regeneration. How this head-tail regeneration polarity decision is made is studied to identify principles underlying tissue-identity specification in regeneration. We report that inhibition of activin-2, which encodes an Activin-like signaling ligand, resulted in the regeneration of ectopic posterior-facing heads following amputation. During tissue turnover in uninjured planarians, positional information is constitutively expressed in muscle to maintain proper patterning. Positional information includes Wnts expressed in the posterior and Wnt antagonists expressed in the anterior. Upon amputation, several wound-induced genes promote re-establishment of positional information. The head-versus-tail regeneration decision involves preferential wound induction of the Wnt antagonist notum at anterior-facing over posterior-facing wounds. Asymmetric activation of notum represents the earliest known molecular distinction between head and tail regeneration, yet how it occurs is unknown. activin-2 RNAi animals displayed symmetric wound-induced activation of notum at anterior- and posterior-facing wounds, providing a molecular explanation for their ectopic posterior-head phenotype. activin-2 RNAi animals also displayed anterior-posterior (AP) axis splitting, with two heads appearing in anterior blastemas, and various combinations of heads and tails appearing in posterior blastemas. This was associated with ectopic nucleation of anterior poles, which are head-tip muscle cells that facilitate AP and medial-lateral (ML) pattern at posterior-facing wounds. These findings reveal a role for Activin signaling in determining the outcome of AP-axis-patterning events that are specific to regeneration. A central problem in animal regeneration is how animals determine what body part to regenerate. Planarians are flatworms that can regenerate any missing body region, and are studied to identify mechanisms underlying regeneration. At transverse amputation planes, a poorly understood mechanism specifies regeneration of either a head or a tail. This head-versus-tail regeneration decision-making process is referred to as regeneration polarity and has been studied for over a century to identify mechanisms that specify what to regenerate. The gene notum, which encodes a Wnt antagonist, is induced within hours after injury preferentially at anterior-facing wounds, where it specifies head regeneration. We report that Activin signaling is required for regeneration polarity, and the underlying asymmetric activation of notum at anterior- over posterior-facing wounds. We propose that Activin signaling is involved in regeneration-specific responses broadly in the animal kingdom.
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