Cellular Regulation in Genitourinary Development

器官及其功能的发育由特定基因的协调表达引起的细胞分化和模式决定。这个奥布莱恩泌尿外科研究中心的竞争性更新集中在调节泌尿生殖道（GU）发育的遗传，分子和细胞事件。四个项目，建立了资深科学家和两个试点的初级研究人员跨越两个临床和一个基础科学部门，十年的生产合作记录提出。项目1（Gomez）研究了一种新的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的序列元件是否决定器官和细胞特异性。项目2（Chevalier）将在一个新开发的新生儿输尿管部分梗阻模型中研究有益和有害作用的介质。翻译研究部分将寻找梗阻性肾病的尿液标志物。早期发现可促进梗阻性肾损伤的恢复。Pilot 1（Roth）将通过检查输尿管平滑肌的胚胎起源和谱系来衔接项目2。将确定不同细胞类型的克隆性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）调查的发展和监管（雄激素），补偿（输精管结扎术），和基因组事件，导致天然抗菌肽，包括防御素，在GU道的合成。项目4（Flickinger）研究涉及音刺猬途径基因的附睾分割的发展和新的后果。Pilot 2（Lysiak）研究了半胱天冬酶2和Bcl-2家族的下游促凋亡成员在确定睾丸中生殖细胞数量中的作用。P50的研究人员有着共同的主题，研究类似的机制，但将注意力集中在GU道内的不同器官上。拟议的研究将推进新的诊断测试和治疗疾病的发展，从肾功能不全到男性不育症，建立在生殖和细胞生物学，泌尿学和儿科肾脏学在弗吉尼亚大学的优势。

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.