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Integrity and localization of Mitochondria in Menkes Disease Pathogenesis

门克斯病发病机制中线粒体的完整性和定位

基本信息

批准号：
10685619
负责人：
Kaela S. Singleton
金额：
$ 8.48万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10685619
关键词：
Address Amino Acids Award Binding Binding Proteins Bioinformatics Cell Maturation Cells Cerebral cortex Co-Immunoprecipitations Coffin-Siris Syndrome Collaborations Communities Complex Cortical Cord Coupled DNA Data Dedications Development Educational process of instructing Educational workshop Embryo Family Family member Foundations Gene Expression Genes Goals High Mobility Group Proteins Home House mice Institution Knowledge Lead Literature Malignant Neoplasms Menkes Kinky Hair Syndrome Mentors Mentorship Methodology Mitochondria Modeling Molecular Motivation Mus Nervous System Neurodevelopmental Disorder Neuronal Differentiation Neuronal Plasticity Neurons Neurosciences Orthologous Gene Pathogenesis Phase Phenocopy Play Positioning Attribute Postdoctoral Fellow Preparation Process Production Property Protein Region Proteins Rana Research Research Personnel Research Project Grants Role Running SOX11 gene Specific qualifier value Spinal Cord System Technical Expertise Techniques Time Training Universities Work Xenopus laevis anticancer research axon regeneration cancer cell differentiation career cell fate specification fascinate innovation malformation member mouse model mutant nerve injury nerve stem cell nervous system development neural repair neurodevelopment neuron development pre-doctoral programs rare genetic disorder skills small molecule stem symposium timeline tool trait transcription factor transcriptome transcriptome sequencing

项目摘要

PROJECT ABSTRACT The development of the nervous system involves the specification of neural progenitors and eventual differentiation into mature neurons. Each step in this process is achieved through changes in cell fate and is coordinated by precise expression and function of transcription factors (TFs). Sox proteins are a large family of TFs that along with partner proteins, regulate the production, differentiation, and maturation of cells in the nervous system. Previous studies have shown that Sox11, a member of the SoxC family, is dynamically expressed in Xenopus laevis (frog) and Mus musculus (mouse) neural development and plays similar roles in promoting neuronal differentiation in each system. While deficits in Sox11 function have been implicated in neurodevelopmental disorders and malformations in the cerebral cortex and spinal cord, molecular mechanisms of Sox11 function remain poorly understood. To address this, the F99 phase of this proposal will investigate Sox11's diverse role in neural development using two models - frog and mouse - in order to characterize Sox11 function in distinct models. Results from these studies will provide critical information about neural development and chages in TF function over evolutionary time, and may provide information on Sox11's potential role in neural injury and plasticity and, possibly, even cancer. Completion of the F99 phase sets a strong intellectual, technical and professional foundation for the postdoctoral (K00) phase of this award. During the K00 phase, training in understanding how neuronal identity is generated and whether deficits may lead to neurodevelopmental disorders will develop knowledge, expertise, and skills essential to becoming an independent investigator.

项目摘要神经系统的发育涉及神经祖细胞的规范和最终的分化为成熟的神经元。这个过程中的每一步都是通过细胞命运的改变来实现的，并且是由转录因子 (TF) 的精确表达和功能协调。 Sox 蛋白是一个大家族转录因子与伙伴蛋白一起调节细胞的产生、分化和成熟神经系统。先前的研究表明，Sox11 作为 SoxC 家族的成员，动态地在非洲爪蟾（青蛙）和小家鼠（小鼠）神经发育中表达，并在促进各系统的神经元分化。虽然 Sox11 功能的缺陷与大脑皮层和脊髓的神经发育障碍和畸形，分子机制 Sox11 的功能仍然知之甚少。为了解决这个问题，该提案的 F99 阶段将调查 Sox11 在神经发育中的不同作用使用青蛙和小鼠两种模型来表征 Sox11 在不同的模型中发挥作用。这些研究的结果将提供有关神经发育的关键信息以及 TF 功能随进化时间的变化，并可能提供有关 Sox11 在神经中潜在作用的信息损伤和可塑性，甚至可能是癌症。 F99阶段的完成奠定了强大的智力、技术基础以及该奖项博士后（K00）阶段的专业基础。在K00阶段，训练了解神经元身份是如何产生的以及缺陷是否可能导致神经发育障碍疾病将培养成为独立调查员所必需的知识、专业知识和技能。