Activin-βA signaling is required for zebrafish fin regeneration
Activin-βA signaling is required for zebrafish fin regeneration
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DOI：
10.1016/j.cub.2007.07.019
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发表时间：
2007-08-21
期刊：
影响因子：
9.2
通讯作者：
Keating, Mark T.
中科院分区：
文献类型：
--
作者：
Jazwinska, Anna;Badakov, Rossen;Keating, Mark T.
脊椎动物肢体再生发生在羊膜动物中，如蝾螈、蝾螈和斑马鱼[1-4]。残肢截肢后，切除部位被伤口表皮覆盖，伤口表皮覆盖在残肢的成熟组织上，胚芽由此产生。胚芽是一团祖细胞，构成一个顶端生长带。在生长形成过程中，近端胚细胞逐渐离开该区域，并进行分化，导致被切除结构的替换。对于损伤后触发再生事件的机制知之甚少。斑马鱼尾鳍为研究再生机制提供了一个有价值的模型[3,5,6]。斑马鱼胚母细胞表达特异性基因，如含有同源盒的转录因子msxBand msxC[7]和分泌信号FGF20a[8]。在这项研究中，我们着手确定在断鳍后和胚形成前转录上调的信号。因此，我们发现一个编码TGF β相关配体的基因激活素- β a （β a行为）在断肢后6小时内在创面边缘以及后期在胚部被强烈诱导。通过两种特定的化学抑制剂SB431542和SB505124抑制激活素信号传导，导致再生的早期和完全阻断。β A及其受体alk4的morpholino敲低会损害再生的进展。对表型的进一步研究表明，激活素信号对于伤口愈合和胚质增殖过程中的细胞迁移是必要的。这些发现揭示了激活素- β a信号在脊椎动物附属物表观遗传再生过程中损伤后的组织修复和随后的外植体形成中的作用。
Vertebrate limb regeneration occurs in anamniotes such as newts, salamanders, and zebrafish [1-4]. After appendage amputation, the resection site is covered by a wound epidermis capping the underlying mature tissues of the stump from which the blastema emerges. The blastema is a mass of progenitor cells that constitute an apical growth zone. During outgrowth formation, the proximal blastemal cells progressively leave the zone and undergo the differentiation that results in the replacement of the amputated structures. Little is known about the mechanisms triggering regenerative events after injury. The zebrafish caudal fin provides a valuable model to study the mechanisms of regeneration [3, 5, 6]. Zebrafish blastemal cells express specific genes, such as the homeobox-containing transcription factors msxBand msxC [7], and secreted signal FGF20a [8]. In this study, we set out to identify signals that are transcriptionally upregulated after fin amputation and before blastema formation. Accordingly, a gene encoding a TGF beta-related ligand, activin-beta A (act beta A), was found to be strongly induced within 6 hr after fin amputation at the wound margin, and later in the blastema. Inhibition of Activin signaling through two specific chemical inhibitors, SB431542 and SB505124, lead to the early and complete block of regeneration. The morpholino knockdown of act beta A and its receptor alk4 impaired the progression of regeneration. Closer examination of the phenotype revealed that Activin signaling is necessary for cell migration during wound healing and blastemal proliferation. These findings reveal a role of Activin-beta A signaling in the tissue repair after injury and subsequent outgrowth formation during epigenetic regeneration of the vertebrate appendage.