How are regenerative cells recruited during zebrafish larval tail regeneration?

斑马鱼幼虫尾部再生过程中再生细胞是如何招募的？

• 批准号: BB/S015086/1
• 负责人: Henry Roehl
• 金额: $ 48.61万
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FS015086%2F1
• 关键词: How; regenerative; cells; recruited; during

Regenerative biology is a scientific field that aims to understand the mechanisms and limitations of regenerative capacity in different organisms. Although mammals are able to heal wounds and regrow many tissues such as skin and muscle, the regeneration of complex structures is limited to the liver, kidney and digit tip. Aquatic vertebrates on the other hand, are able to regenerate large portions of organs including limb, tail, spinal cord, retina and heart. When comparable damage occurs in mammals, tissue fails to regrow and scarring occurs. Organ regeneration in aquatic vertebrates requires many of the same genes that are deployed during the initial development of the organ. This indicates that the reinitiation of developmental genes is important to rebuild the organ. One possible explanation for the poor regenerative potential observed in mammals is that damage does not trigger these developmental genes. These genes are present in mammals but are simply not reactivated. Thus, the elucidation of the mechanism by which tissue damage triggers developmental genes is crucial to further our understanding how successful regeneration takes place. A second reason for poor mammalian regeneration may be a failure to recruit new cells to the site of injury in sufficient numbers to restore the missing tissue. When tissue is damaged in mammals, limited numbers of regenerative cells are attracted to the injury. Studies in aquatic species indicate that large numbers of regenerative cells can be recruited from a diverse array of sources. The identification of the mechanisms that recruit cells to contribute to regeneration in aquatic species may help to facilitate regeneration in mammals by allowing more regenerative cells to be attracted to the damaged site. Our project focuses of zebrafish as a model for regeneration. When a small portion from the end of the tail is removed, the fish regenerate the missing tissue after 3 to 4 days. By studying this process, we have identified a crucial regenerative pathway (called the Hedgehog pathway) that recruits regenerative cells to the site of injury enabling the redevelopment of the tail. In the first part of this project we aim to determine precisely which cells are recruited to repair the damaged tail and what roles do they play during regeneration. In the second part of the project we aim to determine how Hedgehog signalling acts on these cells to initiate regeneration. The knowledge gained from our study will hopefully one day help us to develop new clinical approaches to organ regeneration in humans. Many of the same genes that are active during zebrafish regeneration are found in humans, including those that act in the Hedgehog pathway. This suggests that we may be able to activate the same pathways in humans to mobilise untapped sources of regenerative cells and improve our regenerative capabilities.

再生生物学是一个旨在了解不同生物体再生能力的机制和限制的科学领域。虽然哺乳动物能够愈合伤口并再生许多组织，如皮肤和肌肉，但复杂结构的再生仅限于肝脏，肾脏和指尖。另一方面，水生脊椎动物能够再生大部分器官，包括肢体，尾巴，脊髓，视网膜和心脏。当类似的损伤发生在哺乳动物身上时，组织无法再生，并出现疤痕。 水生脊椎动物的器官再生需要许多在器官最初发育期间部署的相同基因。这表明发育基因的重新启动对器官的重建很重要。在哺乳动物中观察到的再生潜力差的一个可能的解释是，损伤不会触发这些发育基因。这些基因存在于哺乳动物中，但不会被重新激活。因此，阐明组织损伤触发发育基因的机制对于进一步理解成功的再生是至关重要的。 哺乳动物再生不良的第二个原因可能是未能在损伤部位招募足够数量的新细胞来恢复缺失的组织。当哺乳动物的组织受损时，有限数量的再生细胞被吸引到损伤处。对水生物种的研究表明，大量的再生细胞可以从各种来源中招募。识别募集细胞以促进水生物种再生的机制可能有助于通过将更多的再生细胞吸引到受损部位来促进哺乳动物的再生。 我们的项目聚焦于斑马鱼作为再生模型。当尾巴末端的一小部分被切除时，鱼会在3到4天后再生缺失的组织。通过研究这个过程，我们已经确定了一个关键的再生途径（称为刺猬途径），它将再生细胞招募到损伤部位，使尾巴能够重新发育。在这个项目的第一部分，我们的目标是精确地确定哪些细胞被招募来修复受损的尾巴，以及它们在再生过程中扮演什么角色。在该项目的第二部分，我们的目标是确定刺猬信号如何作用于这些细胞，以启动再生。 从我们的研究中获得的知识有望有一天帮助我们开发新的人类器官再生临床方法。许多在斑马鱼再生过程中活跃的基因也在人类中发现，包括那些在刺猬途径中起作用的基因。这表明，我们可能能够激活人类的相同途径，以动员未开发的再生细胞来源并提高我们的再生能力。

项目成果

Tetraspanin Cd9b and Cxcl12a/Cxcr4b have a synergistic effect on the control of collective cell migration.

• DOI: 10.1371/journal.pone.0260372
• 发表时间: 2021
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Marsay KS;Greaves S;Mahabaleshwar H;Ho CM;Roehl H;Monk PN;Carney TJ;Partridge LJ
• 通讯作者: Partridge LJ

Tetraspanin Cd9b and Cxcl12a/Cxcr4b have a synergistic effect on the control of collective cell migration

四跨膜蛋白 Cd9b 和 Cxcl12a/Cxcr4b 对集体细胞迁移的控制具有协同作用

• DOI: 10.1101/2021.05.19.444012
• 发表时间: 2021
• 作者: Marsay K