Cellular Regulation in Genitourinary Development

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。O'Brien泌尿研究中心的这一竞争性更新集中在调节泌尿生殖系统（GU）发育的遗传、分子和细胞事件上。提出了由两个临床和一个基础科学部门建立的四个资深科学家和两个初级研究人员的试点项目，并提出了十年的富有成效的合作记录。项目1 （Gomez）研究了一种新的肾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特异性将被研究。项目2 （Chevalier）将在新开发的新生儿部分输尿管梗阻模型中研究有益和有害作用的介质。转化研究部分将寻找阻塞性肾病的尿标志物。早期发现可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与项目2相吻合。它将确定克隆扩增与不同细胞类型的同步迁移是否有助于输尿管扩张，并将为肾积水疾病提供见解。项目3 （Turner）研究了发育和调节（雄激素），代偿（输精管切除术）和基因组事件导致天然抗菌肽的合成，包括防御素，在GU道。项目4 （Flickinger）研究了涉及超音刺猬通路基因的附睾分割的发展和新结果。Pilot 2 （Lysiak）研究了caspase 2和Bcl-2家族下游促凋亡成员在睾丸中生殖细胞数量的建立中的作用。本P50的研究人员有共同的主题，研究相似的机制，但直接关注GU道内的不同器官。拟议的研究将以弗吉尼亚大学生殖和细胞生物学、泌尿学和儿科肾脏病学的优势为基础，推进从肾功能不全到男性不育症等疾病的新型诊断测试和治疗的发展。

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.