Whitehead Institute for Biomedical Research, Cambridge, MA, United States of America.
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, United States of America.
PLoS Genet. 2021 Mar 29;17(3):e1009466. doi: 10.1371/journal.pgen.1009466. eCollection 2021 Mar.
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.
涡虫是扁形动物，能够进行全身再生。这种能力涉及一种机制，可以区分需要头部再生的面向前方的伤口和需要尾部再生的面向后方的伤口。研究这种头-尾再生极性决定的机制是为了确定组织身份指定在再生中的基本原则。我们报告说，抑制激活素-2（编码一种激活素样信号配体）会导致截肢后再生异位面向后方的头部。在未受伤的涡虫组织更新过程中，位置信息在肌肉中持续表达，以维持正确的模式。位置信息包括在后部表达的 Wnts 和在前部表达的 Wnt 拮抗剂。在截肢后，几个伤口诱导基因促进了位置信息的重新建立。头-尾再生决定涉及在面向前方的伤口中优先诱导 Wnt 拮抗剂 notum，而在面向后方的伤口中则不诱导。notum 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。activin-2 RNAi 动物在前部和后部伤口处均显示出 notum 的对称伤口诱导激活，为其异位后部头部表型提供了分子解释。activin-2 RNAi 动物还表现出前后（AP）轴分裂，两个头部出现在前部芽中，而在后部芽中出现各种头部和尾部组合。这与前极的异位核化有关，前极是头部尖端肌肉细胞，有利于面向后方伤口的 AP 和中侧（ML）模式。这些发现揭示了激活素信号在决定特定于再生的 AP 轴模式事件结果中的作用。
