Characterization of Gli3 function during development of the corpus callosum: a model for the pathogenesis of ACS and GCPS Syndrome

胼胝体发育过程中 Gli3 功能的表征：ACS 和 GCPS 综合征发病机制的模型

• 批准号: 21072571
• 负责人: Privatdozent Dr. Thomas Theil, since 8/2006
• 金额: --
• 依托单位: Centre for Discovery Brain Sciences
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2006
• 资助国家: 德国
• 起止时间: 2005-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/21072571?language=en
• 关键词: Characterization; Gli3; function; during; development

Mental Retardation (MR) is a relatively common form of cognitive impairment affecting 1%- 3% of the population. Understanding the biology of MR is complicated by the extraordinary heterogeneity of MR disorders. Acrocallosal syndrome (ACS) represenst a specific form of MR which is characterized by the absence of the corpus callosum, the mafor fiber tract connecting the left and right cerebral hemisphere. Also, a subset of Greig cephalopolydactyly syndrome (GCPS) patients are mentally retarded and both syndromes can be caused by mutations in the zinc finger transcription factor gene GLI3.My lab has a major interest in characterizing the role of Gli3 during development of the cerebral cortex. In this proposal we want to use Gli3 mutant mice as a model to elucidate the mechanisms leading to the absence of the corpus callosum in these animals and by interference in ACS/GCPS patients. We will use Dil tracing techniques to examine axonal projections of cortical neurons and in situ hybrdization and immunohistochemical analysis to define the molecular and cellular basis for the agenesis of the corpus callosum. From this analysis we expect further clues to our understanding of the causes underlying MR which is ultimatively required for defining potential treatments of MR patients.

精神发育迟滞 (MR) 是一种相对常见的认知障碍形式，影响 1% - 3% 的人口。由于 MR 疾病的非凡异质性，理解 MR 的生物学变得复杂。肢端胼胝体综合征 (ACS) 是 MR 的一种特殊形式，其特征是胼胝体缺失，胼胝体是连接左右大脑半球的纤维束。此外，Greig 头多指综合征 (GCPS) 患者的一部分患有智力障碍，这两种综合征都可能是由锌指转录因子基因 GLI3 的突变引起的。我的实验室的主要兴趣是表征 Gli3 在大脑皮层发育过程中的作用。在本提案中，我们希望使用 Gli3 突变小鼠作为模型来阐明导致这些动物胼胝体缺失以及对 ACS/GCPS 患者的干扰的机制。我们将使用 Dil 追踪技术来检查皮质神经元的轴突投影，并使用原位杂交和免疫组织化学分析来定义胼胝体发育不全的分子和细胞基础。从这一分析中，我们期望获得进一步的线索，帮助我们理解 MR 的根本原因，这最终是确定 MR 患者的潜在治疗方法所必需的。