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Chromatin regulation by BAF complex controls cortical astrogenesis

BAF 复合物的染色质调节控制皮质星形发生

基本信息

批准号：
252505134
负责人：
Dr. Tran Cong Tuoc, Ph.D.
金额：
--
依托单位：
Abteilung für Humangenetik
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2014
资助国家：
德国
起止时间：
2013-12-31 至 2017-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/252505134?language=en
关键词：
Chromatin regulation BAF complex controls

项目摘要

“Astrocytes constitute the largest cell population in the human brain and are crucial for the brain development. Defects in astrogenesis are linked with neurological disorders such as Rett syndrome, fragile X syndrome, and brain tumors. Therefore, it is important to understand how astrocytes are generated.The chromatin remodeling SWI/SNF (SWItch/Sucrose NonFermentable) complex, also known as BAF (Brg1/Brm Associated Factors) complex, plays an essential role in brain development, however, its function in astrogenesis is largely unknown. Our expression analysis indicated that two paralog subunits BAF155 and BAF170 are expressed in all known murine cortical astrocyte sources such as late cortical progenitors (E17.5-E18.5) of the ventricular zone (VZ), adult neural stem cells (aNSCs) in the subventricular zone (SVZ) and dentate gyrus (DG), and dividing astrocytes (also known as astrocyte precursors) in the cortical layers of juvenile mice. In addition, our preliminary proteomic data indicates that the both BAF subunit interacts in vivo with key factors, which were known to play a key role in astrogenesis.The primary aim of this proposal is to characterize the astrocytic phenotypes of BAF155 and BAF170 mutant mice. Secondly, we aim to study the BAF155 and BAF170-dependent mechanisms that control astrocytic development by applying a combination of genomic, proteomic approaches, advanced imaging and genetic manipulation techniques. This study would provide valuable insights into the molecular mechanism, which is mediated by the mSWI/SNF chromatin remodeling complex that controls astrogenesis”.

“星形胶质细胞是人脑中最大的细胞群，对大脑发育至关重要。星形细胞发生的缺陷与神经系统疾病有关，如雷特综合征、脆性X综合征和脑肿瘤。染色质重塑SWI/SNF（SWItch/Sucrose NonFermentable）复合物，又称BAF（Brg 1/Brm Associated Factors）复合物，在脑发育中起着重要作用，但其在星形胶质细胞发生中的作用尚不清楚。我们的表达分析表明，两个副神经元亚基BAF 155和BAF 170在所有已知的小鼠皮质星形胶质细胞来源中表达，如晚期皮质祖细胞（E17.5-E18.5），脑室下区（SVZ）和齿状回（DG）中的成体神经干细胞（aNSC），以及幼年小鼠皮质层中的星形胶质细胞（也称为星形胶质细胞前体）的分裂。此外，我们初步的蛋白质组学数据表明，这两个BAF亚基在体内与关键因子相互作用，这些因子已知在星形发生中起关键作用。其次，我们的目标是研究BAF 155和BAF 170依赖的机制，控制星形胶质细胞的发展，通过应用基因组学，蛋白质组学方法，先进的成像和遗传操作技术相结合。这项研究将为了解控制星形发生的mSWI/SNF染色质重塑复合物介导的分子机制提供有价值的见解”。