IRXB Factors Direct Follicle Maturation

IRXB 直接促进卵泡成熟

• 批准号: 9037517
• 负责人: Joan S Jorgensen
• 金额: $ 31.66万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9037517
• 关键词: Birth; Cell Communication; Cell Death; Cells; Cessation of life; Communication; Cyst; Data; Development; Elements; Ensure; Female; Foundations; Functional disorder; Gene Cluster; Generations; Genetic; Germ Cells; Goals; Gonadal structure; Graafian Follicles; Health; Homeobox; Individual; Infertility; Intervention; Invaded; Knock-in; Knock-out; Knowledge; Laboratories; Life; Modality; Molecular Conformation; Mus; Oocytes; Ovarian; Ovary; Ovulation; Pathway Analysis; Pathway interactions; Patients; Phenotype; Population; Premature Ovarian Failure; Primordial Follicle; Publishing; Reporting; Signal Transduction; Somatic Cell; Staging; Structure of primordial sex cell; Testing; Time; Transcriptional Regulation; Woman; Work; experience; fetal; functional outcomes; granulosa cell; member; molecular dynamics; mouse model; mutant; novel; transcription factor

DESCRIPTION (provided by applicant): The fundamental relationships established between somatic cells and oocytes within germline cysts and primordial follicles during ovary development provide the framework for successful oocyte survival, maturation, and ultimate release upon ovulation. A long-term goal of our work is to discover the pathways and factors that facilitate oocyte-somatic cell communication during ovary development and early follicle formation. This issue is critical for us to develop the means to cultivate oocyte health during follicle development and maturation to ultimately preserve genetic transfer and species survival. The fundamental hypothesis guiding this proposal is that Iroquois homeobox transcription factors, Irx3/5, which are tightly regulated by ¿catenin, coordinate somatic cell-oocyte communication to promote oocyte survival and early stages of follicle maturation. In AIM 1, inducible mouse models will be used to knockout and knock-in gonad Irx3/5 activity to identify their critical juncture of temporal and spatial expression that regulates communication between somatic cells and the oocyte in germline cysts and primordial follicles to promote oocyte health and survival. Then in AIM 2, we will investigate the temporal and spatial transcriptional regulation of Irx3/5 by ¿catenin in somatic and germ cells and the functional outcome of this pathway by evaluating whether re-introduction of Irx3 expression can rescue the germ cell death phenotype in ¿catenin-mutant ovaries. Successful completion of these aims will uncover a novel pathway, ¿catenin-Irx3/5, in the control of oocyte-granulosa cell communication whose disruption may contribute to causes of infertility and premature ovarian failure.

描述（由申请人提供）：卵巢发育过程中种系囊肿和原始卵泡内的体细胞和卵母细胞之间建立的基本关系为卵母细胞的成功存活、成熟和排卵时的最终释放提供了框架。发现在卵巢发育和早期卵泡形成过程中促进卵母细胞与体细胞通讯的途径和因素，这个问题对于我们开发培养卵母细胞健康的方法至关重要。指导该提议的基本假设是易洛魁同源盒转录因子 Irx3/5，它受到 ¿ 的严格调控。连环蛋白，协调体细胞-卵母细胞通讯，促进卵母细胞存活和卵泡成熟的早期阶段。在 AIM 1 中，将使用诱导型小鼠模型敲除和敲入性腺 Irx3/5 活性，以确定其时间和空间表达的关键时刻。调节生殖囊肿和原始卵泡中体细胞与卵母细胞之间的通讯，以促进卵母细胞的健康和存活。然后在 AIM 2 中，我们将研究时间。和 Irx3/5 的空间转录调控 ¿通过评估重新引入 Irx3 表达是否可以挽救 ¿ 中的生殖细胞死亡表型，研究体细胞和生殖细胞中的连环蛋白以及该途径的功能结果成功完成这些目标将揭示一条新的途径，¿连环蛋白-Irx3/5，控制卵母细胞-颗粒细胞通讯，其破坏可能导致不孕和卵巢早衰。