FGF Signaling in Zebrafish Mesonephric Kidney Regeneration

斑马鱼中肾再生中的 FGF 信号传导

• 批准号: 9147469
• 负责人: Thomas Fermin Gallegos
• 金额: $ 6.53万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-01 至 2017-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9147469
• 关键词: Activities of Daily Living; Acute Renal Failure with Renal Papillary Necrosis; Address; Adult; Affect; Alleles; Biological Assay; Biological Models; CRISPR/Cas technology; Cell Lineage; Cell Proliferation; Cell Therapy; Cells; Chronic; Chronic Kidney Failure; DUSP6 protein; Deterioration; Development; Developmental Process; Disease; Dominant-Negative Mutation; Epithelium; Event; Exons; FGF20 gene; FGF8 gene; Fibroblast Growth Factor; Fibroblast Growth Factor Receptors; Fishes; Foundations; Gene Expression; Gene Targeting; Generations; Genes; Genetic; Goals; Growth; Health; Human; In Situ; In Situ Hybridization; Injury; Injury to Kidney; Kidney; Knock-out; Knowledge; Ligands; Longevity; Maintenance; Malignant Neoplasms; Mammals; Mediating; Mesonephric structure; Metronidazole; Modeling; Morphogenesis; Natural regeneration; Nephrons; Nitroreductases; Organ; Organogenesis; Outcome; Patients; Pharmacology; Population; Process; Proliferating; Pronephric structure; Receptor Gene; Regenerative response; Renal function; Renal tubule structure; Reporter; Reproducibility; Reverse Transcriptase Polymerase Chain Reaction; Role; Scheme; Signal Pathway; Signal Transduction; Site; Specificity; Staining method; Stains; Stem cells; Testing; Therapeutic; Time; Tissues; Transgenes; Transgenic Model; Transgenic Organisms; United States; Vesicle; WNT Signaling Pathway; Work; Zebrafish; adult stem cell; base; cell type; conditional mutant; follow-up; genetic analysis; homologous recombination; human disease; human embryonic stem cell; in vivo; induced pluripotent stem cell; inhibitor/antagonist; injured; kidney cell; mature animal; mutant; nephrogenesis; novel; progenitor; public health relevance; receptor; regenerative; regenerative therapy; response; response to injury; stem cell differentiation; stem cell fate specification; success; tissue regeneration

 DESCRIPTION (provided by applicant): The progressive loss of nephrons and deterioration of renal function is a hallmark or several chronic human diseases. The generation of new nephrons in adult kidneys, a goal of many stem cell based inquiries, is best studied in the context of regenerative nephrogenesis in adult animals. This proposal aims to study the role of FGF signaling in the novel context of injury-induced nephrogenesis in the adult zebrafish mesonephros. The specific aims of the proposal will answer the questions: 1. What is the role of FGF signaling in activation and aggregation of adult nephron progenitor cells? 2. What are the FGF ligands and receptors required for kidney regeneration? 3. Genetic analysis of FGF signaling pathways in development and regeneration. FGF signaling is integral to the morphogenesis and identity dynamics of cells in development and disease. FGF signaling is an established regulator of renal tubule growth and is implicated in chronic kidney disease. While mammals lack the ability to produce new nephrons after initial organogenesis, the zebrafish mesonephros continues to produce new nephrons throughout the lifespan. Further, the adult zebrafish pronephros responds to acute kidney injury by rapid and reproducible mass neo- nephrogenesis. This proposed work will utilize this model system to identify important signaling related to the process of adult stem cell activation in renal injury, will provide important information relevant to the utilization of stem cells as therapeutics, and will result in genetic tols for addressing questions related to adult stem cells in the kidney.

 描述（由申请人提供）：肾单位的进行性损失和肾功能恶化是几种慢性人类疾病的标志。成年肾脏中新肾单位的产生是许多基于干细胞的研究的目标，最好在成年动物再生肾发生的背景下进行研究。本研究的目的是研究成纤维细胞生长因子信号在成年斑马鱼中肾损伤诱导的新的肾发生中的作用。该提案的具体目标将回答以下问题：1。FGF信号在成人肾单位祖细胞活化和聚集中的作用是什么？2.肾脏再生所需的FGF配体和受体是什么？3. FGF信号通路在发育和再生中的遗传分析。FGF信号传导对于发育和疾病中细胞的形态发生和身份动力学是不可或缺的。FGF信号传导是肾小管生长的既定调节剂，并且与慢性肾脏疾病有关。虽然哺乳动物在最初的器官发生后缺乏产生新肾单位的能力，但斑马鱼中肾在整个生命周期中继续产生新肾单位。此外，成年斑马鱼原肾通过快速和可重复的大量新肾发生来响应急性肾损伤。这项拟议的工作将利用这个模型系统，以确定重要的信号转导相关的过程中的成人干细胞激活肾损伤，将提供重要的信息，利用干细胞作为治疗，并将导致遗传tols解决问题有关的成人干细胞在肾脏。