Fate of Aggrecan-Expressing Progenitors in Gliogenesis

胶质细胞生成中表达聚集蛋白聚糖的祖细胞的命运

• 批准号: 6673187
• 负责人: Miriam S Domowicz
• 金额: $ 7.26万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6673187
• 关键词: biomarker; cell migration; cell proliferation; chondroitin sulfates; gene expression; genetic promoter element; glia; immunocytochemistry; in situ hybridization; nerve stem cell; neurogenesis; polymerase chain reaction; proteoglycan; tissue /cell culture; transcription factor

DESCRIPTION (provided by applicant): There is no definitive evidence regarding how precursor cells in the neuroepithelium switch from generating neuroblasts to generating glioblasts. Studies on the generation of glia cell types, in particular astrocytes, have been hindered by the lack of markers for their precursors and by their extensive migratory pathways. The principal investigator speculates that the cell-type switched to glioblast is distinguished by the differential expression of specific adhesion and extracellular matrix (ECM) molecules, reflecting the differential expression of transcription factors. The developmentally controlled expression of the aggrecan gene in brain ventricular zones during the active period of neuronal migration and gliogenesis suggests an important role for this molecule in neuronal-glial interactions. However, the specific functions and interactions in which aggrecan is involved in vivo remain unclear and will require further investigation. On the basis of the investigator's preliminary results, two hypotheses can be put forth with respect to the function of aggrecan during this process: 1) changes in the composition and/or structure of the ECM may influence the switching of precursor cells differentiating from neuroblast to glioblast cell-fates, or may influence the final glial phenotype (oligodendrocyte or astrocyte) that the precursors can become, and 2) alternatively, aggrecan may regulate the level of cell proliferation or affect the migration of the precursor cells which populate the brain. In order to distinguish between these possibilities a detailed study of aggrecan expression relative to that of different cell type markers, as well as of modifications in cell fate or proliferation associated with the lack of aggrecan expression in the aggrecan-deficient nanomelic mutant, will be the main focus of this proposal.

描述（由申请人提供）：没有关于神经上皮中的前体细胞如何从生成神经母细胞转变为生成胶质母细胞的明确证据。 由于缺乏其前体细胞标记物及其广泛的迁移途径，对神经胶质细胞类型（特别是星形胶质细胞）生成的研究受到阻碍。 主要研究人员推测，转变为胶质母细胞的细胞类型通过特异性粘附和细胞外基质（ECM）分子的差异表达来区分，反映了转录因子的差异表达。 在神经元迁移和胶质细胞生成的活跃期，聚集蛋白聚糖基因在脑室区的发育控制表达表明该分子在神经元-胶质细胞相互作用中发挥重要作用。 然而，聚集蛋白聚糖在体内参与的具体功能和相互作用仍不清楚，需要进一步研究。 根据研究者的初步结果，可以针对聚集蛋白聚糖在此过程中的功能提出两个假设： 1) ECM 组成和/或结构的变化可能会影响前体细胞从神经母细胞分化为胶质母细胞的转变，或者可能影响前体细胞最终形成的神经胶质细胞表型（少突胶质细胞或星形胶质细胞），2)或者，聚集蛋白聚糖可以调节细胞增殖水平或影响大脑中的前体细胞的迁移。 为了区分这些可能性，对聚集蛋白聚糖表达进行了详细研究 相对于不同细胞类型标记的变化，以及与聚集蛋白聚糖缺陷的纳米体突变体中缺乏聚集蛋白聚糖表达相关的细胞命运或增殖的改变，将是该提案的主要焦点。