Cellular and molecular mechanisms of dendrite pruning in Drosophila

果蝇树突修剪的细胞和分子机制

• 批准号: G0600182/1
• 负责人: Darren Williams
• 金额: $ 70.07万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0600182%2F1
• 关键词: Cellular; molecular; mechanisms; dendrite; pruning

The nervous system needs to be accurately wired together to function properly. During development nerve cells (neurons) often overgrow forming many branches, each of which makes connections with many different cells. Some of these branches are redundant or inappropriate and need to be removed for neural circuits to work well. This removal of branches is termed pruning. We have shown that during metamorphosis fruit flies prune back the branches of their sensory neurons by a local degeneration. This pruning looks very similar to degeneration found in nerves following injury or that seen in diseases like Alzheimer?s. Circulating blood cells remove branches by engulfing (eating) them. Our preliminary data shows that the molecular machinery normally used by a cell to commit ?cellular suicide? (apoptosis) is activated locally in the branches that need to be removed. During apoptosis a cell disassembles itself in an orderly manner and signals to other cells in the body to eat it whole. In pruning neurons this machinery appears to be tightly regulated to prevent the cell dying. Blocking the machinery suppresses the removal of the branches, suggesting that it is important for flagging branches to be eaten by blood cells. The work described here will establish how the ?apoptotic machinery? is switched on in these branches and how this tells the blood cells to eat only those regions of the cell. We hope this will also tell us something about way which neurons degenerate during disease, which could ultimately help cure people. We will make our results available to the public by publishing significant advances on our website, through press releases and by giving talks.

神经系统需要精确地连接在一起才能正常工作。在发育过程中，神经细胞（神经元）经常过度生长，形成许多分支，每个分支与许多不同的细胞连接。其中一些分支是多余的或不合适的，需要删除以使神经回路正常工作。这种树枝的去除被称为修剪。我们已经证明，在变态期间，果蝇通过局部变性修剪其感觉神经元的分支。这种修剪看起来非常类似于损伤后神经中发现的退化，或者类似于阿尔茨海默病的疾病。S.循环中的血细胞通过吞噬树枝来清除树枝。我们的初步数据显示，细胞通常使用的分子机制？细胞自杀细胞凋亡（apoptosis）在需要切除的分支中被局部激活。在凋亡过程中，细胞以有序的方式分解自己，并向体内的其他细胞发出信号，将其整个吃掉。在修剪神经元的过程中，这种机制似乎受到严格的调节，以防止细胞死亡。阻断这一机制会抑制树枝的脱落，这表明血细胞吃掉下垂的树枝是很重要的。这里描述的工作将建立如何？凋亡机制？以及它如何告诉血细胞只吃那些区域的细胞。我们希望这也能告诉我们神经元在疾病期间退化的方式，这最终可以帮助治愈人们。我们将通过在我们的网站上发布重大进展，通过新闻稿和讲座向公众提供我们的结果。