Cellular Regulation in Genitourinary Development

器官的发育及其功能由特定基因的协调表达控制着细胞的分化和模式。奥布莱恩泌尿学研究中心的这一竞争性更新专注于调节生殖道发育的遗传、分子和细胞事件。四个项目由资深科学家完成，两个试点项目由初级研究人员完成，涉及两个临床科室和一个基础科学科室，具有十年的卓有成效的合作记录。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。该基因启动子区域的序列元件是否决定器官和细胞的特异性将被调查。项目2(Chvalier)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影响的介体。一个翻译研究部分将搜索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)将通过研究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性扩张和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洞察。项目3(Turner)研究了在胃肠道中导致天然抗菌肽(包括防御素)合成的发育和调节(雄激素)、代偿(输精管结扎)和基因组事件。项目4(Flickinger)研究了涉及音速刺猬途径基因的附睾分割的发育和新的后果。Pilot 2(Lysiak)研究了半胱氨酸天冬氨酸氨基转移酶2及其下游促凋亡成员在确定睾丸生殖细胞数量中的作用。这个P50的研究人员有共同的主题，研究相似的机制，但将注意力集中在胃束内的不同器官上。拟议中的调查将推动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，为从肾功能不全到男性不育等疾病开发新的诊断测试和治疗方法。

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.