Genetic analysis of hypothalamic tanycyte function

下丘脑单胞功能的遗传分析

• 批准号: 7914208
• 负责人: Seth Blackshaw
• 金额: $ 20.3万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7914208
• 关键词: 4-Hydroxy-Tamoxifen; Ablation; Adult; Alleles; Behavior; Blood - brain barrier anatomy; Cells; Data; Development; Emotional; Future; Gene Expression; Genes; Genetic Recombination; Hypothalamic structure; Injection of therapeutic agent; Knock-in Mouse; Mediating; Metabolic; Mus; Mutagenesis; Mutant Strains Mice; Neuroglia; Neurohormones; Permeability; Physiological; Physiological Processes; Physiology; Process; Radial; Regulation; Reporter; Site; Testing; Transgenic Mice; adult neurogenesis; base; cell type; controlled release; embryonic stem cell; feeding; genetic analysis; homologous recombination; in vivo; nestin protein; public health relevance; selective expression

DESCRIPTION (provided by applicant): Hypothalamic tanycytes have been a cell type in search of a defined function for nearly sixty years. The prominent presence of tanycytes in the mediobasal hypothalamus, the key central regulator for a broad range of appetitive and emotional behaviors, has led to much speculation about their physiological function. A great deal of mostly indirect evidence has been accumulated to suggest their involvement in processes ranging from control of blood-brain barrier permeability, to regulation of neurohormone release and control of feeding, to adult neurogenesis. However, it has so far not been possible to effectively and selectively manipulate the function of tanycytes in vivo, and thus far these proposed functions of tanycytes have not been directed tested. We have identified a set of genes that are selectively expressed in hypothalamic tanycytes. We propose to use this data to generate transgenic mouse lines that will permit both selective and conditional ablation of tanycytes and selective and inducible Cre-based recombination in tanycytes. We will then selectively ablate hypothalamic tanycytes using these lines, and examine the contribution of these cells to aspects of hypothalamic physiology. PUBLIC HEALTH RELEVANCE: Hypothalamic tanycytes have been proposed to regulate many different physiological processes. However, it has thus far not been possible to effectively and selectively manipulate tanycyte function, and thus these proposed functions of tanycytes have not been directly tested. We propose to generate transgenic mice that will allow us to conditionally and selectively manipulate gene expression in hypothalamic tanycytes. We will use these lines to selectively ablate hypothalamic tanycytes and to study the behavior and physiology of mice lacking these cells.

描述（由申请人提供）：下丘脑tanycytes已成为一种细胞类型，用于寻找定义的功能已有近60年了。 tanycytes在地甲状腺下丘脑中的显着存在，这是广泛的开胃菜和情感行为的关键中心调节剂，导致人们对其生理功能进行了很多猜测。已经积累了大量间接证据，以表明它们参与了从控制血脑屏障渗透性的控制，到调节神经激素释放和喂养的控制，再到成人神经发生。但是，到目前为止，尚无对体内tanycytes的功能有效和有选择地操纵的功能，到目前为止，尚未对这些提议的tanycytes功能进行测试。我们已经确定了在下丘脑tanycytes中选择性表达的一组基因。我们建议使用这些数据生成转基因小鼠线，以允许坦率和有条件消融，以及在tanycytes中的选择性和基于CRE的重组。然后，我们将使用这些线选择性地消除下丘脑tanycytes，并检查这些细胞对下丘脑生理学方面的贡献。 公共卫生相关性：已经提出了下丘脑tanycytes来调节许多不同的生理过程。但是，到目前为止，尚无有效和选择性地操纵tanycyte功能的可能性，因此尚未直接测试这些tanycytes的拟议功能。我们建议生成转基因小鼠，这将使我们能够在下丘脑tanycytes中有条件和选择性地操纵基因表达。我们将使用这些线选择性地消除下丘脑tanycytes，并研究缺乏这些细胞的小鼠的行为和生理学。

项目成果

Patterning, specification, and differentiation in the developing hypothalamus.

• DOI: 10.1002/wdev.187
• 发表时间: 2015-09
• 期刊: Wiley interdisciplinary reviews. Developmental biology
• 作者: Bedont JL;Newman EA;Blackshaw S
• 通讯作者: Blackshaw S

A genomic atlas of mouse hypothalamic development.

• DOI: 10.1038/nn.2545
• 发表时间: 2010-06
• 期刊: NATURE NEUROSCIENCE
• 影响因子: 25
• 作者: Shimogori, Tomomi;Lee, Daniel A.;Miranda-Angulo, Ana;Yang, Yanqin;Wang, Hong;Jiang, Lizhi;Yoshida, Aya C.;Kataoka, Ayane;Mashiko, Hiromi;Avetisyan, Marina;Qi, Lixin;Qian, Jiang;Blackshaw, Seth
• 通讯作者: Blackshaw, Seth

Rax regulates hypothalamic tanycyte differentiation and barrier function in mice.

• DOI: 10.1002/cne.23451
• 发表时间: 2014-03
• 期刊: JOURNAL OF COMPARATIVE NEUROLOGY
• 影响因子: 2.5
• 作者: Miranda-Angulo, Ana L.;Byerly, Mardi S.;Mesa, Janny;Wang, Hong;Blackshaw, Seth
• 通讯作者: Blackshaw, Seth