Molecular Mechanisms of Visual Thalamic Development

视觉丘脑发育的分子机制

• 批准号: 7575237
• 负责人: Sam H Horng
• 金额: $ 4.59万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7575237
• 关键词: Age; Auditory; Autistic Disorder; Axon; Binding Sites; Biological Assay; Brain; Candidate Disease Gene; Cell Nucleus; Cells; Cognition Disorders; Complementary DNA; Computer software; Computing Methodologies; DNA Microarray Chip; Dandy-Walker Syndrome; Data; Development; Dorsal; Electroporation; Embryo; Embryonic Development; Eph Family Receptors; Event; Family; Fellowship; Gene Expression; Genes; Genetic; Geniculate body structure; Holoprosencephaly; Human; Immunohistochemistry; In Situ Hybridization; Individual; Knockout Mice; Lateral Geniculate Body; Lead; Ligands; Maps; Medial; Methods; Microarray Analysis; Modality; Molecular; Mus; Mutation; Names; Neonatal; Neurodevelopmental Disorder; Pathway interactions; Pattern; Perinatal; Physiological; Play; Polymerase Chain Reaction; Process; Receptor Gene; Regulation; Retina; Rett Syndrome; Role; Screening Result; Sensory; Signal Transduction; Specificity; Spinal Dysraphism; Stimulus; Synapses; Testing; Thalamic Nuclei; Thalamic structure; Time; Tissue-Specific Gene Expression; Transcription factor genes; Up-Regulation; Visual; Visual Pathways; Visual system structure; Work; Zinc Fingers; area striata; axon guidance; axonal pathfinding; cell type; extrastriate visual cortex; gain of function; in utero; insight; loss of function; member; nervous system disorder; novel; null mutation; optical imaging; overexpression; postnatal; receptor; receptor expression; research study; retinogeniculate; transcription factor

DESCRIPTION (provided by applicant): How brain regions form and establish appropriate connections has critical implications for our understanding of developmental neurologic disorders. A mouse model in which visual sensory axons are re-routed to the auditory region of the thalamus after surgical deafferentation enables us to study potential axon guidance cues to the diencephalon. While axon guidance at the optic disk, tract and tectum has been well studied, little is known about mechanisms mediating ingrowth to thalamus. I will use gene microarrays to identify candidate guidance molecules from differential expression patterns between the visual and auditory thalamus in normal and rewired mice. Two novel candidates, the Zic1 and Zic4 transcription factors, exhibit selective expression within the visual thalamus and potentially regulate the expression of soluble guidance cues, including En-2. I will test whether Zic1 and Zic4 expression is necessary and sufficient for axon targeting using in vitro and in vivo assays. Elucidating the process by which regions of the thalamus acquire normal and novel inputs will inform our mechanistic models of disease involving aberrant pathway formation as well as the potential for plasticity in neural connections after stroke or injury.

描述（由申请人提供）： 大脑区域如何形成并建立适当的连接对于我们理解发育性神经系统疾病具有重要意义。在手术传入神经阻滞后，视觉感觉轴突重新路由至丘脑听觉区域的小鼠模型使我们能够研究间脑的潜在轴突引导线索。虽然视盘、视束和顶盖的轴突引导已得到充分研究，但对于介导丘脑向内生长的机制知之甚少。我将使用基因微阵列从正常小鼠和重组小鼠视觉和听觉丘脑之间的差异表达模式中识别候选引导分子。两个新的候选因子 Zic1 和 Zic4 转录因子在视觉丘脑内表现出选择性表达，并可能调节可溶性引导信号（包括 En-2）的表达。我将使用体外和体内测定来测试 Zic1 和 Zic4 表达对于轴突靶向是否是必要和充分的。阐明丘脑区域获得正常和新输入的过程将为我们涉及异常通路形成的疾病机制模型以及中风或损伤后神经连接的可塑性潜力提供信息。