The role of Id3 as a transcriptional regulator of neuronal differentiation in CNS injury of disease

Id3作为神经元分化转录调节因子在疾病中枢神经系统损伤中的作用

• 批准号: 208413883
• 负责人: Professor Dr. Christian Schachtrup, Ph.D.
• 金额: --
• 依托单位: Anatomie II: Abteilung für Molekulare Embryologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/208413883?language=en
• 关键词: role; Id3; transcriptional; regulator; neuronal

After brain injury or neurologic disease, the ability of the central nervous system (CNS) to regenerate is limited. Neural stem cells (NSCs) have the potential to differentiate into neurons and glia, but neurogenesis is incomplete after CNS disease. The molecular mechanisms regulating neuronal differentiation are not understood. Inhibitor of DNA binding (Id) proteins are key regulators of neuronal differentiation during embryogenesis. We propose to characterize the role of Id3 during neuronal regeneration after injury or neurologic disease. Id3 protein expression is regulated by the TGF-β superfamily, which is up-regulated after blood-brain-barrier (BBB) opening. We will identify the spatial and temporal expression of Id3 in two mouse models with BBB opening: trauma and multiple sclerosis (MS). We will examine the transcriptional machinery Id3 utilizes to determine neuronal and glial fates in vitro and we will genetically inhibit Id3 protein in a mouse model of MS potentially identifying Id3 as a therapeutic target in CNS disease. Understanding the cellular and molecular mechanisms regulating neuronal differentiation in CNS disease is important for the development of novel therapeutic approaches that promote functional regeneration.

脑损伤或神经系统疾病后，中枢神经系统（CNS）的再生能力受到限制。神经干细胞具有向神经元和神经胶质细胞分化的潜能，但在中枢神经系统疾病后神经发生是不完全的。调节神经元分化的分子机制尚不清楚。DNA结合抑制因子（Inhibitor of DNA binding，Id）蛋白是胚胎发育过程中神经元分化的重要调控因子。我们建议的特点Id 3在损伤或神经系统疾病后的神经元再生过程中的作用。Id 3蛋白的表达受TGF-β超家族的调节，其在血脑屏障（BBB）开放后上调。我们将确定Id 3的空间和时间的表达在两个小鼠模型与BBB开放：创伤和多发性硬化症（MS）。我们将研究转录机制Id 3利用体外确定神经元和神经胶质细胞的命运，我们将在MS的小鼠模型中遗传抑制Id 3蛋白，可能将Id 3鉴定为CNS疾病的治疗靶点。了解CNS疾病中调节神经元分化的细胞和分子机制对于开发促进功能再生的新治疗方法非常重要。

项目成果

ID(ealizing) control of adult subventricular zone neural stem/precursor cell differentiation for CNS regeneration

ID（实现）控制成人室下区神经干/前体细胞分化以促进中枢神经系统再生

• DOI: 10.1080/23262133.2016.1223532
• 发表时间: 2016
• 期刊: Neurogenesis
• 作者: Bohrer C;Schachtrup C.
• 通讯作者: Schachtrup C.

Id3 Controls Cell Death of 2B4+ Virus-Specific CD8+ T Cells in Chronic Viral Infection

• DOI: 10.4049/jimmunol.1402607
• 发表时间: 2015-09-01
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Menner, Alexandra J.;Rauch, Katharina S.;Schachtrup, Kristina
• 通讯作者: Schachtrup, Kristina

Id3 Maintains Foxp3 Expression in Regulatory T Cells by Controlling a Transcriptional Network of E47, Spi-B, and SOCS3.

• DOI: 10.1016/j.celrep.2016.11.045
• 发表时间: 2016-12
• 期刊: Cell reports
• 影响因子: 8.8
• 作者: Katharina S. Rauch;Miriam Hils;Ekaterina Lupar;S. Minguet;M. Sigvardsson;M. Rottenberg;A. Izcue;C. S

Instructions from the vascular system - directing neural stem cell fate in health and disease.

血管系统的指令 - 指导神经干细胞在健康和疾病中的命运

• DOI: 10.2174/0929867321666131227162215
• 发表时间: 2014
• 期刊: Current medicinal chemistry
• 影响因子: 4.1
• 作者: Schildge S;Bohrer C;Pfurr S;Mammadzada K;Schachtrup K;Schachtrup C
• 通讯作者: Schachtrup C

The balance of Id3 and E47 determines neural stem/precursor cell differentiation into astrocytes

• DOI: 10.15252/embj.201591118
• 发表时间: 2015-11-12
• 期刊: EMBO JOURNAL
• 影响因子: 11.4
• 作者: Bohrer, Christian;Pfurr, Sabrina;Schachtrup, Christian
• 通讯作者: Schachtrup, Christian