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NOVEL MECHANISM OF NEPHRON EPITHELIALIZATION

肾单位上皮化的新机制

基本信息

批准号：
9908069
负责人：
Rachel Katherine Miller
金额：
$ 23.25万
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 2022-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9908069
关键词：
Actins Adherens Junction Adhesions Affect Biological CRISPR/Cas technology Cadherins Cells Childhood Chronic Kidney Failure Complex Congenital Abnormality Cyst Data Defect Development Diagnosis Doctor of Medicine Doctor of Philosophy E-Cadherin Embryo End stage renal failure Epithelial Epithelial Attachment Epithelial Cells Epithelium Genes Goals Human Image Intercellular Junctions Kidney Maintenance Mediating Mesenchymal Stem Cells Microscopy Morphogenesis Morphology Mus Mutation Nephrons Nutrient Pathway interactions Patients Positioning Attribute Process Proteins Publishing Rana Regenerative Medicine Regulation Renal function Reproducibility Research Resolution Role Shapes Site Testing Time Tissues Urinary tract Vesicle WNT Signaling Pathway Work Xenopus base beta catenin congenital anomaly experimental study genome editing insight kidney malformation loss of function nephrogenesis novel planar cell polarity polymerization prenatal progenitor stem cells trafficking treatment strategy wasting

项目摘要

PROJECT SUMMARY/ ABSTRACT: NOVEL MECHANISM OF NEPHRON EPITHELIALIZATION 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that Daam1, a Wnt/ planar cell polarity effector, and Tuba (Dnmbp) are required for nephron morphogenesis, and unpublished data indicate that they are required for cell junction formation during epithelialization.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：肾细胞上皮化的新机制