TOOLS TO ENHANCE STUDY OF REMAK SCHWANN CELLS

描述（申请人提供）：在周围神经系统中，被称为雪旺细胞的特殊胶质细胞与神经元轴突密切相关。髓鞘化雪旺细胞将其膜反复包裹在单个轴突段上形成髓鞘，而Remak雪旺细胞则包裹多个小口径轴突。这两种类型的雪旺细胞都是由一个共同的未成熟的雪旺细胞前体产生的，尽管重要的问题仍未得到解答，但人们对髓鞘雪旺细胞发育的分子机制了解得更多。由于工具的缺乏，对Remak雪旺细胞的研究受到了很大的阻碍——已知的特异性标记物很少，而且大多数这些标记物也在未成熟的雪旺细胞中表达。此外，没有转基因小鼠允许在雷马克雪旺细胞中基因缺失。本研究的主要目的是测试PNS神经胶质细胞的bacTRAP工具集，并确定成熟Remak Schwann细胞的分子特征。本提案的次要目标是利用bacTRAP分析获得的数据，生成可靠地靶向转基因到Remak Schwann细胞的新试剂，包括用于条件基因缺失的Cre重组酶。

DESCRIPTION (provided by applicant): In the peripheral nervous system, specialized glial cells called Schwann cells exist in intimate association with neuronal axons. Myelinating Schwann cells iteratively wrap their membrane around a single axonal segment to generate the myelin sheath, while Remak Schwann cells envelop multiple small caliber axons. Both types of Schwann cells arise from a common immature Schwann cell precursor, and although important questions remain unanswered, far more is known about the molecular mechanisms that govern the development of myelinating Schwann cells. The study of Remak Schwann cells has been significantly hindered by a paucity of tools - few specific markers are known, and most of these are also expressed by immature Schwann cells. Additionally, there are no transgenic mice that permit genetic deletion in Remak Schwann cells. The main goals of this proposal are to test a bacTRAP toolset for PNS glia, and to define the molecular signature of mature Remak Schwann cells. The secondary goals of this proposal, using data obtained from the bacTRAP analysis, are to generate test new reagents for reliably targeting transgenes to Remak Schwann cells, including Cre recombinase for conditional gene deletion.