zic-1 Expression in Planarian neoblasts after injury controls anterior pole regeneration.
zic-1 Expression in Planarian neoblasts after injury controls anterior pole regeneration.
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DOI：
10.1371/journal.pgen.1004452
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发表时间：
2014-07
期刊：
影响因子：
4.5
通讯作者：
Petersen CP
中科院分区：
文献类型：
--
作者：
Vásquez-Doorman C;Petersen CP
损伤反应促进再生生长的机制尚不清楚。由于新母细胞群体的成体多能干细胞的强大调节，涡虫基本上可以再生任何因受伤而被移除的组织，甚至在斩首后。涉及Wnt抑制剂或Wnt配体的极信号中心的形成分别促进头部或尾部再生，这一过程需要在损伤后早期使用新母细胞。我们使用纯化的新生细胞表达谱来确定前极形成所需的因素。使用这种方法，我们确定了zic-1，一个zic家族转录因子，在头部再生早期伤口附近的新母细胞亚群中被转录激活。随着头部再生的进行，Wnt抑制剂nottum在新形成的前极中表达，表达锌-1的细胞来自新母细胞。RNAi抑制zic-1导致前极notum表达和头部再生失败，但不影响尾巴再生。zic-1的表达需要损伤和典型Wnt信号的抑制，双rnai实验表明，zic-1抑制Wnt信号使头部再生。对新母细胞命运决定因素的分析表明，zic-1控制表达foxd的新母细胞中表达notum的细胞形成前极，并组织随后的生长。特化分化程序通常可能是用于再生生长的组织组织中心的损伤依赖性形成的基础。有些动物能够再生因受伤而受损或切除的器官，这种能力可能需要精确控制促进生长的分泌蛋白质。涡虫是一种扁虫，可以通过调节成体干细胞的活性来再生任何缺失的组织，成体干细胞可以产生任何特化的细胞类型。我们发现zic-1基因在涡虫干细胞中因损伤而被激活，并且是斩首后头部再生所必需的。该基因的产物可能作为一种转录因子，产生细胞，分泌一种促进生长的蛋白质，NOTUM，在再生组织生长的尖端，以组织和实现头部再生。这些结果表明，再生需要专门使用干细胞后代来协调损伤后的新组织生产。
Mechanisms that enable injury responses to prompt regenerative outgrowth are not well understood. Planarians can regenerate essentially any tissue removed by wounding, even after decapitation, due to robust regulation of adult pluripotent stem cells of the neoblast population. Formation of pole signaling centers involving Wnt inhibitors or Wnt ligands promotes head or tail regeneration, respectively, and this process requires the use of neoblasts early after injury. We used expression profiling of purified neoblasts to identify factors needed for anterior pole formation. Using this approach, we identified zic-1, a Zic-family transcription factor, as transcriptionally activated in a subpopulation of neoblasts near wound sites early in head regeneration. As head regeneration proceeds, the Wnt inhibitor notum becomes expressed in the newly forming anterior pole in zic-1-expressing cells descended from neoblasts. Inhibition of zic-1 by RNAi resulted in a failure to express notum at the anterior pole and to regenerate a head, but did not affect tail regeneration. Both injury and canonical Wnt signaling inhibition are required for zic-1 expression, and double-RNAi experiments suggest zic-1 inhibits Wnt signaling to allow head regeneration. Analysis of neoblast fate determinants revealed that zic-1 controls specification of notum-expressing cells from foxD-expressing neoblasts to form the anterior pole, which organizes subsequent outgrowth. Specialized differentiation programs may in general underlie injury-dependent formation of tissue organizing centers used for regenerative outgrowth. Some animals are capable of regenerating organs damaged or removed by injury, and this ability likely requires precise control of secreted proteins that promote growth. Planarians are flatworms that can regenerate any missing tissues by regulating the activity of adult stem cells that can produce any specialized cell type. We identify the zic-1 gene as activated in planarian stem cells by injury and needed for head regeneration after decapitation. This gene's product likely acts as a transcription factor to produce cells that secrete a growth-promoting protein, NOTUM, at the tip of the regenerating tissue outgrowth to organize and enable head regeneration. These results suggest that regeneration requires specialized uses of stem cell descendants to orchestrate new tissue production following injury.
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