权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Molecular and cellular characterization of prominin-like molecules in urodele amphibian - A unique model to study central nervous system regeneration

有尾目两栖动物中 prominin 样分子的分子和细胞特征 - 研究中枢神经系统再生的独特模型

基本信息

批准号：
164395472
负责人：
Dr. Denis Corbeil
金额：
--
依托单位：
IMBA - Institute of Molecular Biotechnology GmbH
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2010
资助国家：
德国
起止时间：
2009-12-31 至 2013-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/164395472?language=en
关键词：
Molecular cellular characterization prominin like

项目摘要

The purpose of this research program is to characterize prominin molecules in urodele amphibian axolotl and to assess whether they can be established as markers of normal and/or provoked neurogenesis in the regenerating central nervous system (CNS). As opposed to mammals, aquatic vertebrate animals have an enormous regenerative ability being able to regenerate a number of complex anatomical structures making them attractive systems for studying mechanisms underlying epimorphic regeneration. However, the cellular and molecular characterization of stem and progenitor cells in lower vertebrates is particularly difficult due to the lack of suitable markers. In mammals, prominin-1 defines a broad range of embryonic and somatic stem and progenitor cells including those of the CNS. Recently, we have identified three distinct prominin molecules in axolotl. Remarkably, one of them (i.e. prominin-1) is upregulated upon tail amputation indicating a potential involvement of prominin–positive cells in spinal cord regeneration. Here we propose to dissect the physiological role of prominins in axolotl, and importantly to determine whether they can be used as cell surface markers for the isolation of rare postembryonic stem cells. To that end, we will perform first a detailed analysis of the general expression of these molecules both in the normal developing and adult animals with special emphasis on neurogenic matrix zones of the postembryonic axolotl. Second, their expression will be further documented in regenerating CNS. Third, we will address their functional aspect, for instance in spinal cord regeneration, by down regulating their expression by antisense-inhibition. Finally, we will investigate whether the neural progenitors in the regenerating spinal cord could be prospectively isolated based on the expression of prominin-1. Taken together, the proposed approach will offer a unique opportunity for prospective identification, characterization and eventual isolation of stem and progenitor cells in lower vertebrates.

本研究计划的目的是表征urodele两栖类蝾螈的神经肽分子，并评估它们是否可以作为正常和/或引起的再生中枢神经系统（CNS）的神经发生的标志物。与哺乳动物相反，水生脊椎动物具有巨大的再生能力，能够再生许多复杂的解剖结构，使其成为研究表型再生机制的有吸引力的系统。然而，由于缺乏合适的标记物，低等脊椎动物中干细胞和祖细胞的细胞和分子表征特别困难。在哺乳动物中，Escherin-1定义了广泛的胚胎和体干细胞和祖细胞，包括CNS的干细胞和祖细胞。最近，我们已经确定了三个不同的美西螈分子。值得注意的是，其中之一（即，tumorin-1）是上调后，尾部截肢，表明在脊髓再生的tumorin阳性细胞的潜在参与。在这里，我们建议解剖的生理作用，在蝾螈，重要的是，以确定它们是否可以作为细胞表面标记物的分离罕见的胚胎后干细胞。为此，我们将首先对这些分子在正常发育和成年动物中的一般表达进行详细分析，特别强调胚胎后蝾螈的神经源性基质区。第二，它们的表达将在再生CNS中被进一步记录。第三，我们将通过反义抑制下调它们的表达来解决它们的功能方面，例如在脊髓再生中。最后，我们将探讨是否可以在再生的脊髓神经祖细胞分离的基础上，表达的Rehlin-1。两者合计，所提出的方法将提供一个独特的机会，前瞻性的识别，表征和最终分离的干细胞和祖细胞在低等脊椎动物。