Combining classical and molecular approaches elaborates on the complexity of mechanisms underpinning anterior regeneration.
Combining classical and molecular approaches elaborates on the complexity of mechanisms underpinning anterior regeneration.
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DOI：
10.1371/journal.pone.0027927
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Aboobaker AA
中科院分区：
文献类型：
--
作者：
Evans DJ;Owlarn S;Tejada Romero B;Chen C;Aboobaker AA
当前涡虫前部再生模型引起前部伤口处低水平 Wnt 信号的建立，通过 TALE 类同源域 PREP 的作用促进前部极性和随后的前部命运的阐述。经典的观察结果是，前部断头比后部断头再生头部更快，这是最早提出在发育背景下沿前后（AP）轴梯度的建议之一。目前的前牙再生模型中并未包含对这种现象的明确理解。这就提出了这样的问题：这种时间梯度的潜在分子和细胞基础是什么，它是否可以用当前的模型来解释，以及理解梯度是否会揭示再生事件。截肢后很早就建立了前牙再生率的差异，并且该梯度取决于刺猬 (Hh) 信号传导的活性。通过 Smed-APC-1(RNAi) 或 Smed-ptc(RNAi) 诱导产生两条尾巴的动物失去了前部命运，但形成了先前描述的异位前脑结构。随后，这些动物形成咽周脑结构，这些结构在 Smed-ptc(RNAi) 中从体内生长出来，建立新的 A/P 轴。将双截肢和羟基脲治疗与 RNAi 实验相结合表明，早期异位脑结构是由未定型的干细胞形成的，这些干细胞在截肢时已进入细胞周期的 S 期。我们的结果详细阐述了当前 AP 轴和大脑再生的简单模型。我们发现刺猬信号梯度的证据可以促进后部命运并暂时抑制前部再生。我们的数据支持具有不同早期和晚期再生阶段的前脑再生模型。这些见解共同开始描绘 AP 轴再生中离散的现有信号、新信号以及后来的稳态信号之间的相互作用。
The current model of planarian anterior regeneration evokes the establishment of low levels of Wnt signalling at anterior wounds, promoting anterior polarity and subsequent elaboration of anterior fate through the action of the TALE class homeodomain PREP. The classical observation that decapitations positioned anteriorly will regenerate heads more rapidly than posteriorly positioned decapitations was among the first to lead to the proposal of gradients along an anteroposterior (AP) axis in a developmental context. An explicit understanding of this phenomenon is not included in the current model of anterior regeneration. This raises the question what the underlying molecular and cellular basis of this temporal gradient is, whether it can be explained by current models and whether understanding the gradient will shed light on regenerative events. Differences in anterior regeneration rate are established very early after amputation and this gradient is dependent on the activity of Hedgehog (Hh) signalling. Animals induced to produce two tails by either Smed-APC-1(RNAi) or Smed-ptc(RNAi) lose anterior fate but form previously described ectopic anterior brain structures. Later these animals form peri-pharyngeal brain structures, which in Smed-ptc(RNAi) grow out of the body establishing a new A/P axis. Combining double amputation and hydroxyurea treatment with RNAi experiments indicates that early ectopic brain structures are formed by uncommitted stem cells that have progressed through S-phase of the cell cycle at the time of amputation. Our results elaborate on the current simplistic model of both AP axis and brain regeneration. We find evidence of a gradient of hedgehog signalling that promotes posterior fate and temporarily inhibits anterior regeneration. Our data supports a model for anterior brain regeneration with distinct early and later phases of regeneration. Together these insights start to delineate the interplay between discrete existing, new, and then later homeostatic signals in AP axis regeneration.
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影响因子：
2.7
作者：
Gurley KA;Elliott SA;Simakov O;Schmidt HA;Holstein TW;Sánchez Alvarado A
通讯作者：
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作者：
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通讯作者：
Child, CM
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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