How are regenerative cells recruited during zebrafish larval tail regeneration?

再生生物学是一门旨在了解不同生物体再生能力的机制和局限性的科学领域。尽管哺乳动物能够愈合伤口并再生皮肤和肌肉等许多组织，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，包括四肢、尾巴、脊髓、视网膜和心脏。当哺乳动物出现类似的损伤时，组织不能再生，就会形成疤痕。水生脊椎动物的器官再生需要许多在器官最初发育过程中部署的相同基因。这表明，发育基因的重新启动对重建器官非常重要。在哺乳动物身上观察到的弱再生潜力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身上，但根本没有被重新激活。因此，阐明组织损伤触发发育基因的机制对于我们进一步了解再生是如何成功发生至关重要。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修复丢失的组织。当哺乳动物的组织受到损伤时，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，可以从不同的来源招募大量的再生细胞。确定招募细胞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。我们的项目将斑马鱼作为再生的典范。当尾巴末端的一小部分被移除时，鱼会在3到4天后再生丢失的组织。通过对这一过程的研究，我们已经确定了一条关键的再生途径(称为Hedgehog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，我们的目标是准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Hedgehog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朝一日帮助我们开发新的人类器官再生的临床方法。在人类身上发现了许多在斑马鱼再生过程中活跃的相同基因，包括那些作用于刺猬途径的基因。这表明，我们可能能够激活人类中相同的途径，以动员未开发的再生细胞来源，并提高我们的再生能力。

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.