Extensive and diverse patterns of cell death sculpt neural networks in insects.
Extensive and diverse patterns of cell death sculpt neural networks in insects.
复制标题
细胞死亡的广泛而多样的模式雕刻昆虫中的神经网络。
DOI：
10.7554/elife.59566
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发表时间：
2020-09-07
期刊：
影响因子：
7.7
通讯作者：
Williams DW
中科院分区：
文献类型：
--
作者：
Pop S;Chen CL;Sproston CJ;Kondo S;Ramdya P;Williams DW
神经网络结构和功能的变化被认为是动物行为进化适应的基础。在产生变化的许多发育现象中，程序性细胞死亡（PCD）似乎起着关键作用。我们发现，细胞死亡在昆虫神经发生过程中不断发生，并在神经元出生后不久发生。模仿进化的作用，增加细胞数量，我们人为地阻止PCD的内侧成神经细胞系的果蝇，这导致在生产的“不死”的神经元与复杂的arborisations和不同的神经递质的身份。这些“不死”神经元的激活和行为动物的神经活动记录表明它们是功能性的。专注于两个双翅目在进化过程中失去了飞行，我们发现，飞行interneurons的人口减少可能是由于在发展过程中增加细胞死亡。我们的研究结果表明，基于死亡的模式的进化调制可以产生新的网络配置。就像雕塑家在一块花岗岩上雕刻雕像一样，神经系统在发育过程中通过程序性细胞死亡消除神经元，从而达到成熟状态。在脊椎动物中，这种机制通常涉及新生神经元萎缩和死亡，如果它们在发育过程中无法与其他神经元连接。大多数对昆虫的研究都集中在变态时发生的神经元死亡，在幼虫到成虫的过渡期间，当新的生命阶段不再需要的细胞被淘汰时。波普等人利用一种新设计的遗传探针指出，在果蝇中，变态时神经元的程序性细胞死亡并不是细胞死亡的主要机制。相反，大多数细胞死亡发生在神经元出生的整个幼虫阶段，当大多数成年神经系统建成时。为了进一步了解这种“早期”细胞死亡的作用，神经元被阻止死亡，表明这些细胞能够达到成熟和功能。总之，这些结果表明，早期细胞死亡可能是一种经过进化微调的机制，以塑造昆虫的许多不同的神经系统。为了探索这一点，波普等人在不能飞的果蝇亲属中寻找早期细胞死亡的线索：敏捷的虱子和蜜蜂虱子。这项分析表明，早期细胞死亡可能发生在这两种昆虫中，但它遵循与果蝇不同的模式，可能针对这些果蝇祖先中控制飞行的神经元。大脑是进化的产物：了解神经元如何改变它们的连接和适应可以帮助我们了解大脑在健康和疾病中的工作方式。这些知识也可能与人工智能的工作有关，人工智能是一门学科，通常将人工“大脑”的构建模块和连接建立在神经元如何相互交流的基础上。
Changes to the structure and function of neural networks are thought to underlie the evolutionary adaptation of animal behaviours. Among the many developmental phenomena that generate change programmed cell death (PCD) appears to play a key role. We show that cell death occurs continuously throughout insect neurogenesis and happens soon after neurons are born. Mimicking an evolutionary role for increasing cell numbers, we artificially block PCD in the medial neuroblast lineage in Drosophila melanogaster, which results in the production of ‘undead’ neurons with complex arborisations and distinct neurotransmitter identities. Activation of these ‘undead’ neurons and recordings of neural activity in behaving animals demonstrate that they are functional. Focusing on two dipterans which have lost flight during evolution we reveal that reductions in populations of flight interneurons are likely caused by increased cell death during development. Our findings suggest that the evolutionary modulation of death-based patterning could generate novel network configurations. Just like a sculptor chips away at a block of granite to make a statue, the nervous system reaches its mature state by eliminating neurons during development through a process known as programmed cell death. In vertebrates, this mechanism often involves newly born neurons shrivelling away and dying if they fail to connect with others during development. Most studies in insects have focused on the death of neurons that occurs at metamorphosis, during the transition between larva to adult, when cells which are no longer needed in the new life stage are eliminated. Pop et al. harnessed a newly designed genetic probe to point out that, in fruit flies, programmed cell death of neurons at metamorphosis is not the main mechanism through which cells die. Rather, the majority of cell death takes place as soon as neurons are born throughout all larval stages, when most of the adult nervous system is built. To gain further insight into the role of this ‘early’ cell death, the neurons were stopped from dying, showing that these cells were able to reach maturity and function. Together, these results suggest that early cell death may be a mechanism fine-tuned by evolution to shape the many and varied nervous systems of insects. To explore this, Pop et al. looked for hints of early cell death in relatives of fruit flies that are unable to fly: the swift lousefly and the bee lousefly. This analysis showed that early cell death is likely to occur in these two insects, but it follows different patterns than in the fruit fly, potentially targeting the neurons that would have controlled flight in these flies’ ancestors. Brains are the product of evolution: learning how neurons change their connections and adapt could help us understand how the brain works in health and disease. This knowledge may also be relevant to work on artificial intelligence, a discipline that often bases the building blocks and connections in artificial ‘brains’ on how neurons communicate with one another.