Forkhead Factor, FOXL2, in Pituitary Development

叉头因子 FOXL2 在垂体发育中的作用

• 批准号: 6740488
• 负责人: Buffy Sue Ellsworth
• 金额: $ 4.3万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-30 至 2006-04-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6740488
• 关键词: enzyme mechanism; gel mobility shift assay; gene expression; gene mutation; gene targeting; genetic regulatory element; genetically modified animals; histogenesis; in situ hybridization; laboratory mouse; pituitary gland; postdoctoral investigator; tissue /cell culture; transcription factor; transfection /expression vector

DESCRIPTION (provided by applicant): Foxl-2 is expressed in the developing eye and in the adult ovary and is required for normal development and function of these organs in humans. Recently, expression of FoxL2 has been detected in the developing mouse pituitary from e10.5 to el 5. To examine the role of FOXL2 in pituitary development, the following studies will be performed: characterize the developmental expression of Foxl2 and place it in the genetic hierarchy of pituitary developmental control, define important regulatory sequences for Foxl2 expression in cell culture and transgenic mice, and examine the role of FOXL2 in the developing anterior pituitary by generation of gain and loss of function alleles. In situ hybridization of pituitaries from normal mice will be used to characterize Foxl2 expression. Normal expression patterns for Foxl2 will be compared to those in mice with mutations in critical pituitary transcription factors. This information will place FOXL2 in the genetic hierarchy. Transient transfections of mammalian cells and electrophoretic mobility shift assays will be used to define the minimal essential sequence for Foxl2 expression and to test for direct regulation by factors that are upstream of Foxl2 in the genetic hierarchy. These findings will be confirmed in transgenic animals. To delineate the role of FOXL2 in pituitary development, FoxL2 will be over-expressed and will be disrupted specifically in the pituitaries of mice, allowing us to separate the role of FOXI.2 in the pituitary from its role in other organs.

描述（由申请人提供）：Foxl-2 在发育中的眼睛和成人卵巢中表达，并且是人类这些器官的正常发育和功能所必需的。最近，在发育中的小鼠垂体中从e10.5到el 5中检测到了FoxL2的表达。为了研究FOXL2在垂体发育中的作用，将进行以下研究：表征Foxl2的发育表达并将其置于垂体发育控制的遗传层次中，定义细胞培养物和转基因小鼠中Foxl2表达的重要调控序列，并研究FOXL2在发育中的垂体前叶中的作用 通过功能等位基因的获得和丧失的产生。正常小鼠垂体的原位杂交将用于表征 Foxl2 表达。 Foxl2 的正常表达模式将与关键垂体转录因子发生突变的小鼠的表达模式进行比较。该信息将把 FOXL2 置于遗传层次中。哺乳动物细胞的瞬时转染和电泳迁移率变动测定将用于定义Foxl2表达的最小必需序列并测试遗传层次中Foxl2上游因子的直接调节。这些发现将在转基因动物中得到证实。为了描述 FOXL2 在垂体发育中的作用，FoxL2 将在小鼠垂体中过度表达并被特异性破坏，从而使我们能够将 FOXI.2 在垂体中的作用与其在其他器官中的作用分开。