Molecular Mechanisms of Visual Thalamic Development

描述（由申请人提供）： 大脑区域如何形成和建立适当的连接对我们理解发育性神经障碍具有重要意义。一个小鼠模型，其中视觉感觉轴突被重新路由到听觉区域的丘脑手术后去传入，使我们能够研究潜在的轴突引导线索间脑。虽然在视盘，束和顶盖的轴突导向已经得到了很好的研究，很少有人知道有关的机制介导的向内生长到丘脑。我将使用基因微阵列从正常和重新连接小鼠的视觉和听觉丘脑之间的差异表达模式中识别候选指导分子。两个新的候选人，Zic 1和Zic 4转录因子，表现出选择性表达的视觉丘脑内，并可能调节可溶性的指导线索，包括En-2的表达。我将测试是否Zic 1和Zic 4表达是必要的，并充分利用在体外和体内测定轴突靶向。阐明丘脑区域获得正常和新输入的过程将为我们的疾病机制模型提供信息，包括异常通路形成以及中风或损伤后神经连接可塑性的潜力。

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.