A conserved strategy for inducing appendage regeneration in moon jellyfish, Drosophila, and mice.
A conserved strategy for inducing appendage regeneration in moon jellyfish, Drosophila, and mice.
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DOI：
10.7554/elife.65092
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发表时间：
2021-12-07
期刊：
影响因子：
7.7
通讯作者：
Goentoro L
中科院分区：
文献类型：
--
作者：
Abrams MJ;Tan FH;Li Y;Basinger T;Heithe ML;Sarma A;Lee IT;Condiotte ZJ;Raffiee M;Dabiri JO;Gold DA;Goentoro L
肢体再生可以诱导吗？很少有人研究过这个问题，进化保守的策略还没有出现。这项研究报告了一种诱导附肢再生反应的策略，该策略适用于跨越动物生殖发育的三个物种。在刺胞动物中，用氨基酸L-亮氨酸和生长激素胰岛素喂养月亮水母奥雷利亚的附件再生频率增加。在昆虫中，同样的策略诱导了成年果蝇的胫骨再生。最后，在哺乳动物中，L-亮氨酸和蔗糖给药诱导成年小鼠的手指再生，包括显着的中趾骨截肢。L-亮氨酸和胰岛素/糖的保守效应表明能量参数在再生诱导中的关键作用。营养补充可以诱导附肢再生的简单性提供了一个可在动物中验证的假设。动物替换受损或丢失的组织（或“再生”）的能力是一个滑动尺度，有些动物能够再生整个肢体，而另一些动物只能留下疤痕。但是，为什么有些动物可以再生，而另一些动物的能力则更为有限，这一点多年来一直困扰着科学界。像查尔斯达尔文和奥古斯特魏斯曼这样的人认为再生只在一个特定的器官中进化。相比之下，托马斯摩根认为，所有动物都配备了再生的工具，但在是否能够激活这些过程方面有所不同。如果后者是真的，那么就有可能“开启”再生。那些在一生中不断生长并且不调节体温的动物更有可能再生。但是生长和温度调节有什么共同点呢？两者都是高度能源密集型的，温度调节可能会从其他过程中转移能量。因此，一个问题就出现了：肢体再生是否可以通过为动物提供更多的能量来启动，无论是以糖或氨基酸等营养物质的形式，还是通过给予它们胰岛素等生长激素？Abrams、Tan、Li等人通过切断水母、苍蝇和老鼠的四肢来验证这一假设，然后在它们愈合的八周内向它们的饮食中补充蔗糖（一种糖）、亮氨酸（一种氨基酸）和/或胰岛素。通常情况下，水母在失去一只手臂时会重新排列剩余的手臂，而果蝇则不知道会再生肢体。家鼠通常只能再生被截肢的手指的尖端。但在Abrams，Tan，Li et al.在他的实验中，亮氨酸和胰岛素补充剂刺激了水母和成年果蝇的肢体再生，亮氨酸和蔗糖补充剂使小鼠从第二个关节以下再生出手指。虽然没有在所有动物中观察到再生，但这些结果表明，通过给动物喂食额外的糖和氨基酸，可以诱导再生，并且可以相对容易地完成再生。这些发现强调了通过操纵它们的饮食来增加不同动物的能量供应，而它们正在从截肢中恢复，可以帮助再生。这可能在未来为组织和器官再生的新治疗方法铺平道路。
Can limb regeneration be induced? Few have pursued this question, and an evolutionarily conserved strategy has yet to emerge. This study reports a strategy for inducing regenerative response in appendages, which works across three species that span the animal phylogeny. In Cnidaria, the frequency of appendage regeneration in the moon jellyfish Aurelia was increased by feeding with the amino acid L-leucine and the growth hormone insulin. In insects, the same strategy induced tibia regeneration in adult Drosophila. Finally, in mammals, L-leucine and sucrose administration induced digit regeneration in adult mice, including dramatically from mid-phalangeal amputation. The conserved effect of L-leucine and insulin/sugar suggests a key role for energetic parameters in regeneration induction. The simplicity by which nutrient supplementation can induce appendage regeneration provides a testable hypothesis across animals. The ability of animals to replace damaged or lost tissue (or ‘regenerate’) is a sliding scale, with some animals able to regenerate whole limbs, while others can only scar. But why some animals can regenerate while others have more limited capabilities has puzzled the scientific community for many years. The likes of Charles Darwin and August Weismann suggested regeneration only evolves in a particular organ. In contrast, Thomas Morgan suggested that all animals are equipped with the tools to regenerate but differ in whether they are able to activate these processes. If the latter were true, it could be possible to ‘switch on’ regeneration. Animals that keep growing throughout their life and do not regulate their body temperatures are more likely to be able to regenerate. But what do growth and temperature regulation have in common? Both are highly energy-intensive, with temperature regulation potentially diverting energy from other processes. A question therefore presents itself: could limb regeneration be switched on by supplying animals with more energy, either in the form of nutrients like sugars or amino acids, or by giving them growth hormones such as insulin? Abrams, Tan, Li et al. tested this hypothesis by amputating the limbs of jellyfish, flies and mice, and then supplementing their diet with sucrose (a sugar), leucine (an amino acid) and/or insulin for eight weeks while they healed. Typically, jellyfish rearrange their remaining arms when one is lost, while fruit flies are not known to regenerate limbs. House mice are usually only able to regenerate the very tip of an amputated digit. But in Abrams, Tan, Li et al.’s experiments, leucine and insulin supplements stimulated limb regeneration in jellyfish and adult fruit flies, and leucine and sucrose supplements allowed mice to regenerate digits from below the second knuckle. Although regeneration was not observed in all animals, these results demonstrate that regeneration can be induced, and that it can be done relatively easily, by feeding animals extra sugar and amino acids. These findings highlight increasing the energy supplies of different animals by manipulating their diets while they are healing from an amputated limb can aid in regeneration. This could in the future pave the way for new therapeutic approaches to tissue and organ regeneration.