Novel Mechanism of Nephron Epithelialization

肾单位上皮化的新机制

基本信息

批准号：
10253477
负责人：
Rachel Katherine Miller
金额：
$ 7.8万
依托单位：
UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10253477
关键词：
Actins Biological Cadherins Cells Childhood Congenital Abnormality Data Defect Development Diagnosis Embryo End stage renal failure Epithelial Epithelial Attachment Goals Intercellular Junctions Kidney Mediating Morphogenesis Nephrons Nutrient Regenerative Medicine Renal function Research Role Testing Urinary tract Work congenital anomaly experimental study insight kidney malformation nephrogenesis nephron progenitor novel planar cell polarity polymerization prenatal regenerative tissue stem cells treatment strategy wasting

Actins Biological Cadherins Cells Childhood Congenital Abnormality Data Defect Development Diagnosis Embryo End stage renal failure Epithelial Epithelial Attachment Goals Intercellular Junctions Kidney Mediating Morphogenesis Nephrons Nutrient Regenerative Medicine Renal function Research Role Testing Urinary tract Work congenital anomaly experimental study insight kidney malformation nephrogenesis nephron progenitor novel planar cell polarity polymerization prenatal regenerative tissue stem cells treatment strategy wasting

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项目摘要

PROJECT SUMMARY/ ABSTRACT: NOVEL MECHANISM OF NEPHRON EPITHELIALIZATION (from original R01 proposal) Although congenital anomalies of the kidney and urinary tract (CAKUT) are the predominant birth defects diagnosed in the prenatal period and are the most common cause of pediatric end stage renal disease, only 13% of cases have a known monogenic cause. CAKUT results in defects in the formation of nephrons, which are required for the function of the kidney. Thus, the overall goal this research is to understand how nephron progenitor cells form cell junctions to facilitate tubule epithelialization and morphogenesis. Prior work demonstrates that Daam1, a Wnt/ planar cell polarity effector, and Tuba (Dnmbp) are required for nephron morphogenesis, and unpublished data indicate that they are required for cell junction formation during epithelialization. Thus, the goal of this proposal is to determine how they facilitate cell junction formation in the nephron progenitor cells. The proposed experiments will test the hypothesis that Daam1 and Tuba enable the formation of stable cell junctions during epithelialization and subsequent morphogenesis of the developing nephrons. The hypothesis will be tested through the following aims: Aim 1. Assess the role of Daam1 in the establishment of cell junctions underlying nephric tubulogenesis. The hypothesis that Daam1-mediated actin polymerization regulates the formation of cadherin-mediated contacts that facilitate epithelialization of nephric tubules will be tested. Completion of this aim will provide insight into the previously unrecognized role of Daam1 in nephron epithelialization. Aim 2. Define the role of Tuba in cell junction formation during nephrogenesis. The proposed experiments will test the hypothesis that Tuba is required for epithelial junction formation in the developing nephron. Completion of this aim will uncover whether Tuba facilitates junction formation in epithelializing nephrons. Overall, the experiments proposed in this application will facilitate a new understanding of the cell biological mechanisms contributing to epithelialization and morphogenesis of nephric tubules.

项目摘要/摘要：肾单位化的新型机制（来自原始R01提案）尽管肾脏和尿路的先天异常（Cakut）是主要的先天缺陷在产前期间被诊断出，是小儿终末期肾脏疾病的最常见原因 13％的病例具有已知的单基因原因。 cakut导致形成肾脏的缺陷，这是肾功能所必需的。因此，这项研究的总体目标是了解肾单位祖细胞形成细胞连接，以促进小管上皮化和形态发生。先前的工作证明nephron需要DAAM1，Wnt/ Planar细胞极性效应子和TUBA（DNMBP）形态发生，未发表的数据表明，它们是细胞连接形成所必需的上皮化。因此，该提案的目的是确定它们如何促进细胞连接形成肾单位祖细胞。提出的实验将测试DAAM1和TUBA的假设上皮化和随后形态发生过程中稳定细胞连接的形成肾单位。该假设将通过以下目的进行检验：目标1。评估DAAM1在建立肾小管肾小管基础的细胞连接。 DAAM1介导的肌动蛋白的假设聚合调节钙粘蛋白介导的接触的形成，促进肾脏上皮化小管将进行测试。完成此目标的完成将提供对以前未认识到的作用的见解 nephron上皮化中的daam1。 AIM 2。定义图巴在细胞连接形成中的作用肾病。提出的实验将测试上皮连接需要大小管的假设发育中的肾单位形成。完成此目标的完成将揭示图巴是否促进交界处上皮化肾脏中的形成。总体而言，本应用程序中提出的实验将有助于新的了解有助于上皮化和形态发生的细胞生物学机制小管。