Cellular Regulation in Genitourinary Development

泌尿生殖发育中的细胞调节

• 批准号: 6925393
• 负责人: WILLIAM DONALD STEERS
• 金额: $ 90.13万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6925393
• 关键词: cell growth regulation; histogenesis; reproductive system; urinary tract

The development of organs and their function is governed by the differentiation and patterning of cells through the coordinated expression of specific genes. This competitive renewal for an O'Brien Urology Research Center is focused on the genetic, molecular and cellular events that regulate genitourinary (GU) tract development. Four projects by established senior scientists and two pilots by junior investigators spanning two clinical and one basic science department with a ten-year record of productive collaboration are proposed. Project 1 (Gomez) examines the role of a novel kidney-specific gene in proximal tubular cell maturation and function. Whether sequence elements in the promoter region of this gene determine organ and cell specificity will be investigated. Project 2 (Chevalier) will study the mediators of both salutary and injurious effects in a newly developed model of neonatal partial ureteral obstruction. A translational research component will search for urinary markers for obstructive nephropathy. Early detection may enhance recovery from obstructive renal injury. Pilot 1 (Roth) will dovetail on Project 2 by examining the embryonic origin and lineage of ureteral smooth muscle. It will be determined whether clonal expansion versus synchronous migration of differing cell types contributes to ureteral expansion and will offer insight into hydronephrotic disorders. Project 3 (Turner) investigates the developmental and regulatory (androgenic), compensatory (vasectomy), and genomic events leading to the synthesis of natural antibacterial peptides, including defensins, in the GU tract. Project 4 (Flickinger) examines development and novel consequences of epididymal segmentation involving sonic hedgehog pathway genes. Pilot 2 (Lysiak) investigates the role of caspase 2 and downstream pro-apoptotic members of the Bcl-2 family in establishing the number of germ cells in the testis. Investigators in this P50 share common themes and study similar mechanisms yet direct attention on different organs within the GU tract. The proposed investigations will advance the development of novel diagnostic tests and therapies for disorders ranging from renal insufficiency to male infertility building on strengths in reproductive and cell biology, urology and pediatric nephrology at the University of Virginia.

器官的发育及其功能是由细胞的分化和模式通过特定基因的协调表达来控制的。奥布莱恩泌尿学研究中心的这一竞争性更新重点关注调节泌尿生殖 (GU) 道发育的遗传、分子和细胞事件。提出了由资深科学家发起的四个项目和由初级研究人员发起的两个试点项目，涵盖两个临床部门和一个基础科学部门，并拥有十年富有成效的合作记录。项目 1 (Gomez) 检查一种新型肾脏特异性基因在近端肾小管细胞成熟和功能中的作用。将研究该基因启动子区域的序列元件是否决定器官和细胞特异性。项目 2（Chevalier）将研究新开发的新生儿部分输尿管梗阻模型中有益和有害影响的调节因素。转化研究部分将寻找阻塞性肾病的尿液标志物。早期发现可以促进梗阻性肾损伤的恢复。试点 1（罗斯）将通过检查输尿管平滑肌的胚胎起源和谱系来配合项目 2。将确定不同细胞类型的克隆扩张与同步迁移是否有助于输尿管扩张，并将提供对肾积水疾病的深入了解。项目 3（特纳）研究导致 GU 道中天然抗菌肽（包括防御素）合成的发育和调节（雄激素）、代偿（输精管切除术）和基因组事件。项目 4 (Flickinger) 研究了涉及音刺猬通路基因的附睾分割的发展和新后果。 Pilot 2 (Lysiak) 研究了 caspase 2 和 Bcl-2 家族下游促凋亡成员在确定睾丸中生殖细胞数量方面的作用。该 P50 的研究人员有着共同的主题并研究相似的机制，但将注意力直接集中在 GU 道内的不同器官上。拟议的研究将利用弗吉尼亚大学在生殖和细胞生物学、泌尿学和儿科肾病学方面的优势，推动针对从肾功能不全到男性不育等疾病的新型诊断测试和疗法的开发。