TOOLS TO ENHANCE STUDY OF REMAK SCHWANN CELLS

描述（由申请人提供）：在外周神经系统中，称为许旺细胞的特化神经胶质细胞与神经元轴突密切相关。髓鞘形成施旺细胞反复地将其膜包裹在单个轴突节段周围以产生髓鞘，而Remak施旺细胞包裹多个小口径轴突。这两种类型的许旺细胞都来自一种共同的未成熟许旺细胞前体，尽管重要的问题仍未得到解答，但人们对支配髓鞘形成许旺细胞发育的分子机制了解得更多。Remak Schwann细胞的研究受到缺乏工具的严重阻碍-很少有特异性标记物是已知的，其中大多数也由未成熟的Schwann细胞表达。此外，没有允许Remak Schwann细胞中基因缺失的转基因小鼠。该提案的主要目标是测试PNS神经胶质细胞的bacTRAP工具集，并定义成熟Remak Schwann细胞的分子特征。该提案的第二个目标是使用从bacTRAP分析获得的数据，生成用于可靠地将转基因靶向Remak Schwann细胞的测试新试剂，包括用于条件基因缺失的Cre重组酶。 公共卫生相关性：神经系统中专门的细胞间相互作用的一个极好的例子是神经胶质细胞与轴突的密切联系。在外周神经中，Remak Schwann细胞是一类未充分研究的神经胶质细胞，尽管越来越清楚这些细胞是神经再生和疾病病理学的关键介质。在这项提案中，我们将开发研究Remak Schwann细胞所急需的工具，包括用于测量其基因表达的新工具，用于在这种细胞类型中产生Cre介导重组的转基因小鼠的新分子标记物和试剂。

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. PUBLIC HEALTH RELEVANCE: An exquisite example of specialized cell-cell interactions in the nervous system is the intimate association of glial cells with axons. In the peripheral nerve, Remak Schwann cells are an understudied class of glial cell, although it is increasingly clear that these cells are critical mediators of nerve regeneration and disease pathology. In this proposal, we will develop much-needed tools for the study of Remak Schwann cells, including new tools for measuring their gene expression, new molecular markers and reagents for generating transgenic mice for Cre mediated recombination in this cell type.