Cell signaling in regeneration and tissue scaling

项目摘要/摘要 具有再生能力的生物已经成为揭示自然机制的信息模型 哪种组织损伤会激活干细胞或祖细胞进行损伤修复。时间、地点和范围 损伤不是预先确定的，需要存在指导组织修复活动的机制 这完美地抵消了损害的影响。理解这一过程的一个关键问题是再生能力如何。 组织重新定义了因受伤而移除的区域，并假设这与迄今尚未发现的情况有关 在大范围内强有力地调节组织比例的系统。开始解决这个问题 问题是，必须定义构成区域认同和比例的细胞信号系统 成长。虽然再生组织已经被广泛地探讨了损伤诱导信号和 干细胞或祖细胞的参与，对分子和发育过程知之甚少 能够在受伤后恢复体型，并在成年后保持体型。在这个目标中 格兰特，这一赤字是通过利用脊椎动物系统中的专业知识来解决的，这一系统独特地允许 研究通过再生调节组织重新缩放的信号，以阐明调节和 损伤后产生和恢复组织相称性的发育机制。揭开面纱 生物体用来控制组织比例的基本机制将提供基本的见解 了解生长失调的疾病、比例生长的本质和茎的控制 用于组织再生的细胞。

Project Summary/Abstract Organisms with regenerative abilities have been informative models for uncovering natural mechanisms by which tissue damage activates stem or progenitor cells for injury repair. The timing, location, and extent of injuries are not predetermined, requiring the existence of mechanisms that instruct tissue restoration activities that perfectly counter the effects of damage. A key question to understand this process is how regenerative tissue redefines territories removed by injury, and it is hypothesized this is related to as-yet undiscovered systems that robustly regulate tissue proportionality across large length scales. To begin to address this question, it is essential to define the cell signaling systems that underlie regional identity and proportional growth. While regenerative tissues have been extensively probed for the roles of injury-induced signals and the involvement of stem or progenitor cells, much less is known about the molecular and developmental processes that enable the restoration of form after injury and its maintenance through adult growth. In the aims of this grant, this deficit is addressed by leveraging expertise in the planarian system, which uniquely allows for the study of signaling that regulates re-scaling of tissues through regeneration, to elucidate the regulatory and developmental mechanism that generates and restores tissue proportionality after injury. Uncovering fundamental mechanisms used by organisms to control tissue proportionality will provide foundational insights into understanding diseases of growth misregulation, the nature of proportional growth, and the control of stem cells for tissue regeneration.