Identification and characterization of regulators of neuronal differentiation during planarian regeneration

涡虫再生过程中神经元分化调节因子的鉴定和表征

• 批准号: 152045553
• 负责人: Professorin Dr. Kerstin Bartscherer
• 金额: --
• 依托单位: Department Biological Sciences and Biotechnology
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/152045553?language=en
• 关键词: Identification; characterization; regulators; neuronal; differentiation

Planarians are freshwater flatworms that have the remarkable talent to regrow lost body parts, even the head. This phenomenon is due to a high number of neoblasts, adult stem cells that can differentiate into any planarian cell type at the wound. Even though planarians are therefore an emerging model for stem cell biology, little is known about which signals specify neoblast fate and trigger their differentiation. The recent availability of a sequenced genome in combination with RNAi enables us now to study planarian gene function on a largescale basis. We plan to use RNAi in planarians to identify regulators and organizers of the regenerating nervous system. As cell-to-cell communication depends on secreted factors, we will generate an RNAi library against all secreted proteins encoded in the planarian genome. By systematic knockdown of these genes and subsequent analysis of the regenerating nervous system with neuron-specific antibodies, we hope to identify novel regulators of neuronal differentiation and growth. Novel proteins will be analyzed in secondary assays for their molecular functions, expression patterns, interaction partners, and their conservation and function in higher organisms such as frogs and Drosophila.

浮游生物是淡水扁虫，具有再生失去的身体部位，甚至头部的非凡天赋。这种现象是由于伤口处有大量的新生成体干细胞，可以分化成任何类型的扁平类细胞。因此，尽管浮游生物是干细胞生物学的一个新兴模型，但关于哪些信号决定了新生细胞的命运并触发了它们的分化，人们知之甚少。最近测序的基因组与RNAi相结合，使我们现在能够在大规模的基础上研究脊椎动物的基因功能。我们计划在行星动物身上使用RNAi来识别再生神经系统的调节者和组织者。由于细胞间的通讯依赖于分泌因子，我们将针对脊椎动物基因组中编码的所有分泌蛋白建立RNAi文库。通过系统地敲除这些基因，并随后用神经元特异性抗体分析再生神经系统，我们希望识别神经分化和生长的新调节因子。新的蛋白质将在二次分析中分析它们的分子功能、表达模式、相互作用伙伴以及它们在青蛙和果蝇等高等生物中的保守性和功能。