Semaphorin/plexin interactions in regenerative neurogenesis in zebrafish

斑马鱼再生神经发生中信号蛋白/丛蛋白的相互作用

• 批准号: BB/T015594/1
• 负责人: Thomas Becker
• 金额: $ 64.78万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FT015594%2F1
• 关键词: Semaphorin; plexin; interactions; regenerative; neurogenesis

After spinal cord injury, nerve cells are lost and never replaced. Attempts to replace the lost nerve cells are met with limited success in mammalian models. Alternatively, dormant stem cells, which do exist in mammals, could be reactivated to produce new nerve cells, but these cells do not receive the right signal in the injured spinal cord. In contrast, zebrafish stem cells are reactivated after injury and produce nerve cells that are integrated in the injured spinal cord, and fish fully recover from paralysis. As any injury, spinal cord injury elicits an inflammatory reaction, and we have previously shown that this is necessary for regeneration of nerve cells in the zebrafish. However, the identity of the molecular signals that are received by the stem cells in the injured nervous system are unclear. We have analysed the genes that are expressed in single immune cells and stem cells and found specific matching signal (semaporins) and receptor genes (plexins) to be present. Here, we want to test whether this signal/receptor interaction is crucial for regeneration of nerve cells in zebrafish, by mutating the genes in turn and determine whether regeneration is impaired. This research can thus identify the 'language' in which immune cells communicate with spinal stem cells to bring about regeneration. Ultimately, similar signals may be used in therapeutic approaches to instruct the stem cells in mammals to produce nerve cells after an injury and thus bring about repair.

脊髓损伤后，神经细胞丢失，永远不会被取代。在哺乳动物模型中，试图取代失去的神经细胞的尝试取得了有限的成功。或者，哺乳动物中确实存在的休眠干细胞可以被重新激活以产生新的神经细胞，但这些细胞在受损的脊髓中无法接收正确的信号。相反，斑马鱼干细胞在受伤后被重新激活，并产生整合在受伤脊髓中的神经细胞，鱼类完全从瘫痪中恢复。与任何损伤一样，脊髓损伤引起炎症反应，我们以前已经证明这是斑马鱼神经细胞再生所必需的。然而，受损神经系统中干细胞接收的分子信号的身份尚不清楚。我们已经分析了在单个免疫细胞和干细胞中表达的基因，并发现存在特定的匹配信号（信号蛋白）和受体基因（丛蛋白）。在这里，我们想测试这种信号/受体相互作用是否对斑马鱼神经细胞的再生至关重要，通过依次突变基因并确定再生是否受损。因此，这项研究可以确定免疫细胞与脊髓干细胞沟通以实现再生的“语言”。最终，类似的信号可以用于治疗方法，指导哺乳动物的干细胞在损伤后产生神经细胞，从而进行修复。

项目成果

Regenerative neurogenesis: the integration of developmental, physiological and immune signals.

• DOI: 10.1242/dev.199907
• 发表时间: 2022-04-15
• 期刊: Development (Cambridge, England)