Specifying the Neocortical Area Map in the Ferret

指定雪貂的新皮质区域图

• 批准号: 8623674
• 负责人: ELIZABETH Elizabeth Grove
• 金额: $ 22.25万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8623674
• 关键词: Address; Age; Animals; Area; Benchmarking; Birth; Brain; Cell Death; Cell Proliferation; Cells; Defect; Development; Disease; Dominant-Negative Mutation; Dorsal; Electroporation; Embryo; Evolution; FGF8 gene; Ferrets; Fibroblast Growth Factor 8; Fibroblast Growth Factor Receptors; Gene Expression; Gene Expression Profile; Generations; Genes; Goals; Health; Human; Immunohistochemistry; In Situ Hybridization; Life; Light; Mammals; Maps; Memory; Mental disorders; Modeling; Molecular; Motor; Mus; Neocortex; Neurons; Newborn Infant; Pattern; Perception; Positioning Attribute; Primordium; Procedures; Process; Relative (related person); Research; Role; Sensory; Shapes; Signal Transduction; Site; Source; Specific qualifier value; Staging; Stem cells; Structure; Telencephalon; Testing; Tissues; Transcription factor genes; Transfection; Ventricular; Work; base; cranium; design; discount; expectation; fluorescence imaging; in utero; morphogens; mouse model; neocortical; nervous system disorder; postnatal; progenitor; programs; protein expression; public health relevance; pup; research study; subventricular zone; transcription factor

Project Summary/Abstract My overall goal is to understand how the neocortical area map develops in the embryonic and early postnatal mammalian brain. The prevailing model of how area patterning is initiated in the embryo is based on research in the smooth-brained or "lissencephalic" mouse, yet studies that support this model are aimed at revealing how the area map is established in mammals in general. Recent discoveries regarding the generation of cortical neurons in gyrencephalic mammals, however, suggest problems with applying the mouse model to these species. A major concern in the field, therefore, is that there can be no "general" model of neocortical patterning. I propose here to test whether the current model holds for area map development in the gyrencephalic cortex of the ferret. First, I will verify that the ferret cortical primordium (CP) has similar signaling centers to those that pattern the cortex in the mouse. I predict this will be so, given that one center has already been identified in humans. Further, I will identify which of the gene and protein expression patterns that delineate areas in the postnatal mouse cortex also delineate area boundaries in ferret. In the mouse telencephalon, a rostral patterning center (RPC) releases Fibroblast Growth Factor (FGF) 8, a morphogen that disperses in a gradient across the CP supplying positional values to cortical progenitor cells. I expect the embryonic ferret cortex to have an RPC, which patterns both cortical and subcortical structures. In utero microelectroporation (IUME) will be used in live ferret embryos to manipulate levels of FGF8 at the RPC, and to introduce new sources of FGF8 in the CP. The area map will be examined in the pups at 3 weeks, using gene and protein expression patterns to identify area boundaries. If FGF8 controls the ferret area map, as in the mouse, then augmenting the rostral FGF8 source will shift area boundaries caudally, enlarging rostral areas, and shrinking caudal areas. Depleting the source will have opposite effects, and introducing a new source of FGF8 will duplicate areas. This project is designed to address a major stumbling block in the field of cortical development, and to (re)introduce the ferret as a species in which to investigate the mechanisms that pattern the neocortical area map. A full appreciation of human cortical development in the embryo will aid in understanding several major human neurological and psychiatric disorders with a strong developmental component.

项目摘要/摘要 我的总体目标是了解新皮质区域图是如何在胚胎和 哺乳动物出生后早期的大脑。中启动面积图案的主流模型 胚胎是基于对大脑光滑或无脑小鼠的研究，但研究表明 支持这一模型的目的是揭示哺乳动物的区域地图是如何在 将军。关于脑回皮质神经元生成的最新发现 然而，哺乳动物提出了将老鼠模型应用于这些物种的问题。一个 因此，该领域的主要担忧是，不可能有新皮质的“通用”模型 图案化。我建议在这里测试当前的模型是否适用于在 雪貂的回脑皮质。首先，我将验证雪貂皮质原基(CP) 其信号中心与小鼠大脑皮质的信号中心相似。我预测这将是 因此，鉴于已经在人类身上发现了一个中心。此外，我将确定哪一位 描述出生后小鼠皮质区域的基因和蛋白质表达模式 还可以在雪貂中划定区域边界。在小鼠的端脑中，有一个吻状纹饰中心 (RPC)释放成纤维细胞生长因子(FGF)8，这是一种以梯度方式分散的形态因子 向皮质祖细胞提供位置值。我期待着胚胎 雪貂皮质有一个RPC，它有皮质和皮质下结构的图案。在子宫内 微电穿孔(IUME)将用于活的雪貂胚胎，以操纵FGF8的水平 RPC，并在CP中引入FGF8的新来源。这张地区地图将在 幼崽出生3周时，使用基因和蛋白质表达模式来识别区域边界。如果 FGF8控制雪貂区域地图，就像鼠标一样，然后增加嘴部的FGF8源 会使区域边界向尾部移动，扩大吻部区域，缩小尾部区域。 耗尽来源将产生相反的效果，而引入新的FGF8来源将 重复区域。该项目旨在解决以下领域的主要绊脚石 皮质发育，并(重新)引入雪貂作为一种研究 形成新皮质区域地图的机制。 充分了解人类在胚胎中的皮质发育将有助于理解 几种主要的人类神经和精神疾病具有很强的发展 组件。