F31 Microtubule function in the onset of whole-body regeneration

项目摘要 组织再生是更新、恢复和生长的过程，使生物体重新生长 伤后的肢体和器官。组织再生能力存在于不同的生物体中，这表明它们 可能已经很古老了，所以控制再生的机制对于理解很重要。的 淡水扁虫Schmidteamidiomedicleea几乎可以从任何手术损伤中再生，包括 斩首，是一个模型，了解动物再生的机制基础。受伤后，组织 伤口附近的信号传递给附近的成体多能干细胞，称为成新细胞， 缺失组织的细胞类型高度保守的Wnt信号通路对于控制再生至关重要 前与后的组织身份在涡虫再生。正面对反面最早的事件 确定是损伤诱导的分泌的Wnt抑制剂notum选择性地在前向表达 而不是面向后的伤口部位。然而，指导这种对称性破缺事件的机制是 未知损伤诱导的背核表达发生在具有以下特征的体壁肌细胞的索马体中： 纵向排列的肌纤维，表明肌细胞的方向和极性在发病中的作用， 再生然而，调节这种极性的分子信号和结构是未知的，但经典的 在涡虫中的小分子抑制研究表明微管在该过程中可能起作用。的目标 本项目旨在揭示微管参与再生极性的机制。 具体目标如下。目的1利用RNAi检测微管调节因子的作用 在肌肉中表达，以控制组织再生开始时损伤诱导的基因表达。Aim 2用途 用RNAi进行上位性分析，以揭示驱动蛋白微管马达蛋白与 a用于再生的头部和眼睛区域化的Wnt途径。这些实验将提供洞察力， 损伤诱导再生过程中微管的细胞和分子机制。我的结果将提供 新的见解，了解其他必要的因素，适当的伤害信号，并帮助形成更好的 了解什么调节极性。

Project Summary Tissue regeneration is the process of renewal, restoration and growth that allows an organism to re-grow limbs and organs after injury. Tissue regeneration abilities are present in diverse organisms, suggesting they may have been ancient, so the mechanisms controlling regeneration have been important to understand. The freshwater planarian flatworm Schmidtea mediterranea regenerates from nearly any surgical injury, including decapitation, and is a model for understanding the mechanistic basis of animal regeneration. After injury, tissue near wound sites signals to nearby adult pluripotent stem cells called neoblasts, which differentiate to replace all cell types of missing tissue. The highly conserved Wnt signaling pathway is essential for controlling regeneration of anterior-versus-posterior tissue identity in planarian regeneration. The earliest event in head versus tail determination is the injury induced expression of the secreted Wnt inhibitor notum selectively at anterior-facing and not posterior-facing wound sites. However, the mechanism directing this symmetry breaking event is unknown. Injury induced notum expression occurs from the soma of body wall muscle cells possessing longitudinally aligned muscle fibers, suggesting a role of muscle cell orientation and polarity in the onset of regeneration. However, the molecular signals and structure regulating this polarity are unknown, but classic small molecule inhibition studies in planaria suggest a possible role for microtubules in this process. The goal of this project is to uncover the mechanisms by which microtubules participate in the polarity of the regeneration response in the following specific aims. Aim 1 utilizes RNAi to test roles for microtubule regulatory factors expressed in muscle to control injury-induced gene expression at the onset of tissue regeneration. Aim 2 uses epistasis analysis with RNAi to uncover the mechanism by which a kinesin microtubule motor protein relates to a Wnt pathway for head and eye regionalization used in regeneration. These experiments will provide insight on the cellular and molecular mechanism of microtubules during injury induced regeneration. My results will provide new insights into understanding the other factors necessary for proper injury signal and help form a better understanding on what regulates polarity.