MOLECULAR REGULATION OF GLIAL MATRIX PROTEIN EXPRESSION

胶质基质蛋白表达的分子调控

• 批准号: 2609708
• 负责人: DIANE M JAWORSKI
• 金额: $ 8.58万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-12-12 至 2001-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2609708
• 关键词: astrocytes; cell differentiation; cell migration; extracellular matrix proteins; gene expression; glia; laboratory rat; neurogenesis; protein structure function

DESCRIPTION: The elucidation of the mechanisms of cell migration during central nervous system (CNS) development is important to number of issues in neurobiology. Although the phenomenon of neuronal cell migration has been appreciated for more than a century, identification of The molecular components regulating neuronal cell migration is only beginning to emerge. While neurogenesis occurs in a systematic laminar progression, the mechanisms underlying glial cell dispersion within the CNS are not well understood, and the molecules involved in glial cell migration are yet to be elucidated. In the last several years, our appreciation of the extracellular matrix (ECM) of the CNS has grown. The brain ECM consists of a heterogeneous mixture of glycoconjugates, including the glycosaminoglycan hyaluronan (HA). HA regulates the local cellular environment by facilitating permeability and retention of low molecular weight solutes, while excluding other macromolecules. In a number of systems, including the developing CNS, HA has been implicated in cell and tissue specific functions, including the regulation of cell proliferation, differentiation and migration. HA is the only glycosaminoglycan not covalently associated with core protein; therefore, functions ascribed to HA are likely mediated by proteins which bind HA. We recently identified the gene for a new ECM protein, BEHAB (Brain Enriched HyAluronan-Binding). BEHAB represents the only tissue specific HA-binding protein reported to date. BEHAB mRNA expression is restricted to the CNS. BEHAB mRNA is expressed at high levels when astrocytes proliferate and migrate - during rat brain development, in the reactive gliosis induced by CNS injury and during glioma invasion. These observations have led to the hypothesis we propose to test: that the expression of BEHAB plays a role in regulating astrocyte differentiation and motility in the CNS. Thus far, we have characterized the expression of the BEHAB gene at the mRNA level. The BEHAB cDNA encodes putative secretedHA-binding protein. To ascertain the function of BEHAB, it will be necessary to determine the expression pattern of the extracellular protein product of the BEHAB gene. The first specific aim of this project is to characterize th distribution and regulation of the BEHAB protein during CNS development. BEHAB mRNA is expressed in primary rat astrocyte cultures. However, different levels of BEHAB are expressed by astrocytes derived from different brain areas and from different developmental stages. The second specific aim of this project is to determine how BEHAB expression is regulated. BEHAB mRNA is expressed at high levels during periods of astrocyte cell differentiation and migration. The third specific aim of this project is to test whether BEHAB plays a role in astrocyte differentiation and migration.

描述：阐明细胞迁移机制期间的机制 中枢神经系统（CNS）开发对于数量 神经生物学。 尽管神经元细胞迁移的现象已经 鉴定分子的标识超过一个世纪 调节神经元细胞迁移的成分才开始出现。 尽管神经发生发生在系统的层流进展中，但 中枢神经系统内神经胶质细胞分散的机制不好 理解，与神经胶质细胞迁移有关的分子尚未 阐明。 在过去的几年中，我们对 中枢神经系统的细胞外基质（ECM）已生长。 大脑ECM由 糖缀合物的异质混合物，包括糖胺聚糖 Hyaluronan（HA）。 HA通过 促进渗透性和低分子量溶质的保留， 同时排除其他大分子。 在许多系统中，包括 开发CNS，HA与细胞和组织特异性有关 功能，包括调节细胞增殖，分化 和迁移。 HA是唯一不可避免关联的糖胺聚糖 与核心蛋白；因此，归因于HA的功能可能是介导的 通过结合HA的蛋白质。 我们最近确定了一种新的ECM蛋白的基因Behab（脑富集 透明质酸结合）。 Behab代表唯一的组织特异性HA结合 蛋白质报道迄今为止。 Behab mRNA表达仅限于中枢神经系统。 当星形胶质细胞增殖和 迁移 - 在大鼠脑发育期间，在由 中枢神经系统损伤和神经胶质瘤入侵期间。 这些观察结果导致了 我们建议测试假设：behab的表达在 调节中枢神经系统中星形胶质细胞分化和运动。 到目前为止，我们 已经表征了Behab基因在mRNA水平上的表达。 这 Behab cDNA编码推定的分泌结合蛋白。 确定 Behab的功能，必须确定表达模式 Behab基因的细胞外蛋白产物。 第一个特定 该项目的目的是表征分布和调节 CNS发育过程中Behab蛋白质。 Behab mRNA在主要中表达 大鼠星形胶质细胞培养物。 但是，不同级别的behab由 来自不同大脑区域的星形胶质细胞和不同的星形胶质细胞 发展阶段。 该项目的第二个具体目的是 确定如何调节Behab表达。 Behab mRNA在 星形胶质细胞分化和迁移时期的高水平。 该项目的第三个具体目的是测试Behab是否扮演角色 在星形胶质细胞分化和迁移中。