Genetic Interactions at the Cortical Striatal Border

皮质纹状体边界的遗传相互作用

• 批准号: 7761717
• 负责人: Laura A Cocas
• 金额: $ 2.31万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-02-01 至 2010-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7761717
• 关键词: Adult; Amygdaloid structure; Cadherins; Cell Separation; Cell surface; Cells; Cellular Morphology; Characteristics; Corpus striatum structure; Defect; Development; Dorsal; ETV1 gene; Embryo; Event; Family; Gene Expression; Gene Family; Generations; Genes; Genetic; Genetic Markers; Immunohistochemistry; In Situ Hybridization; Lateral; Limbic System; Maintenance; Mus; Nuclear Structure; Pattern; Play; Reading; Regulation; Role; Side; Source; Stream; Structure; Telencephalon; Transgenic Mice; cell type; insight; loss of function; nerve stem cell; postnatal; transcription factor

DESCRIPTION (provided by applicant): We propose to elucidate the genetic mechanisms that contribute to patterning of ceils at the cortical-striatal border (CSB), a transient boundary in the developing telencephalon. The CSB is a source of cells that migrate to the basal telencephalic limbic system along the lateral cortical stream (LCS). Understanding the genetic patterning of this region will provide insight into the generation of cells that contribute to the amygdala. We hypothesize that the Ets family transcription factors (Er81 and Erm) and the secreted molecules Tgfa and Fgf7 are genetic downstream targets of the Gsh2/Pax6 patterning events that initially establish the border. We hypothesize that Fgf7 and Tgfa have specific roles in maintenance of border characteristics, and/or specification of neural progenitor cells that are generated at the CSB, via regulation of the Ets genes. Thus, transgenic mice lacking Fgf7 and Tgfa will display disrupted expression of Er81 and Erm, as well as other markers of the CSB (e.g. Sfrp2 and Dbx1), resulting in an alteration of the LCS and subsequent disruption of amygdala development. We will use in situ hybridization for specific genetic markers of the border and immunohistochemistry for cellular subtypes to explicate these patterning events.

描述（由申请人提供）：我们建议阐明有助于皮质-纹状体边界（CSB）细胞模式形成的遗传机制，CSB是发育中端脑的短暂边界。 CSB 是沿着侧皮质流 (LCS) 迁移到基底端脑边缘系统的细胞来源。了解该区域的遗传模式将有助于深入了解有助于杏仁核的细胞的生成。我们假设 Ets 家族转录因子（Er81 和 Erm）以及分泌分子 Tgfa 和 Fgf7 是最初建立边界的 Gsh2/Pax6 模式事件的遗传下游目标。我们假设 Fgf7 和 Tgfa 通过调节 Ets 基因，在维持边界特征和/或 CSB 生成的神经祖细胞的规范中具有特定作用。因此，缺乏 Fgf7 和 Tgfa 的转基因小鼠将表现出 Er81 和 Erm 以及 CSB 的其他标记（例如 Sfrp2 和 Dbx1）的表达破坏，导致 LCS 的改变以及随后杏仁核发育的破坏。我们将使用原位杂交来检测边界的特定遗传标记，并使用免疫组织化学来检测细胞亚型，以解释这些模式事件。