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

• 批准号: 10168887
• 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
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10168887
• 关键词: Address; Amino Acids; Award; Binding; Binding Proteins; Bioinformatics; Cell Maturation; Cells; Cerebral cortex; Co-Immunoprecipitations; Coffin-Siris Syndrome; Collaborations; Communities; Complex; Coupled; DNA; Data; Development; Educational process of instructing; Educational workshop; Embryo; Family; Family member; Foundations; Gene Expression; Genes; Goals; High Mobility Group Proteins; Home environment; House mice; Institution; Knowledge; Lead; Literature; Malignant Neoplasms; Menkes Kinky Hair Syndrome; Mentors; Mentorship; Methodology; Mitochondria; Modeling; Molecular; Motivation; Mus; Nervous system structure; 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; TimeLine; Training; Universities; Work; Xenopus laevis; anticancer research; axon regeneration; cancer cell differentiation; career; fascinate; injury and repair; innovation; invention; malformation; member; mouse model; mutant; nerve injury; nerve stem cell; nervous system development; neurodevelopment; neuron development; pre-doctoral; programs; rare genetic disorder; skills; small molecule; stem; symposium; tool; trait; transcription factor; transcriptome; transcriptome sequencing

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特化， 分化为成熟的神经元。这个过程中的每一步都是通过改变细胞命运来实现的， 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， TF与伴侣蛋白沿着调节细胞的产生、分化和成熟， 神经系统以前的研究表明，Sox 11是SoxC家族的一员， 在非洲爪蟾（蛙）和小家鼠（小鼠）神经发育中表达，并在 促进每个系统中的神经元分化。虽然Sox 11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 Sox 11的功能仍然知之甚少。为了解决这个问题，本提案的F99阶段将调查 Sox 11在神经发育中的不同作用使用两种模型-青蛙和小鼠-以表征Sox 11 在不同的模型中运行。这些研究的结果将提供有关神经发育的关键信息 随着进化时间的推移，TF功能的变化，并可能提供Sox 11在神经系统中的潜在作用的信息。 损伤和可塑性甚至可能是癌症完成F99阶段集强大的智力、技术 和专业的博士后（K 00）这个奖项的阶段的基础。在K 00阶段， 了解神经元身份是如何产生的，以及缺陷是否会导致神经发育障碍。 疾病将发展成为一名独立调查员所必需的知识，专业知识和技能。