Receptor tyrosine kinase signaling in astrocyte migration and angiogenesis

星形胶质细胞迁移和血管生成中的受体酪氨酸激酶信号传导

基本信息

批准号：
10734124
负责人：
Chenqi Tao
金额：
$ 41.13万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-30 至 2028-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10734124
关键词：
Ablation Actins Adaptor Signaling Protein Angiogenic Factor Astrocytes Behavior Binding Blood Vessels Blood-Retinal Barrier Coloboma Data Development Disease Endothelial Cells Endothelium Eye Development Eye diseases Family Fibroblast Growth Factor Fibroblast Growth Factor Receptors Future Genes Genetic Glaucoma Gliosis Goals Growth Factor Guanosine Triphosphate Phosphohydrolases Health Homeostasis Image Impairment Invaded Knock-out Ligands MAP Kinase Gene Maintenance Mediating Molecular Mutant Strains Mice Neonatal Nervous System Nuclear Orphan PIK3CG gene Pathway interactions Physiology Platelet-Derived Growth Factor Platelet-Derived Growth Factor Receptor Play Polymers Receptor Protein-Tyrosine Kinases Retina Retinal Ganglion Cells Retinopathy of Prematurity Role Signal Pathway Signal Transduction Source Testing Tissues Vascularization angiogenesis autocrine cell motility cohort migration mouse model mutant neural paracrine polymerization recruit rho scaffold single-cell RNA sequencing transcription factor transcriptomics transmission process

项目摘要

PROJECT SUMMARY Retinal astrocytes form the integral part of the neural-glial-vascular network in the retina. They contribute to the establishment of the retinal vasculature, maintenance of the blood-retina barrier and health of retinal ganglion cells. Although several signaling pathways are known to be active in astrocytes, how they are integrated to regulate astrocyte development and physiology is still poorly understood. This project will investigate the role and mechanism of PDGF and FGF signaling, two closely related receptor tyrosine kinase pathways, in astrocyte development. By generating mouse mutants and performing living imaging, we will delineate the PDGF signaling cascade specific to astrocytes and understand how it regulates the migratory behaviors of astrocytes. Furthermore, we will investigate the molecular mechanism of FGF signaling in regulating astrocyte maturation. Lastly, we will test the hypothesis that FGF and PDGF signaling are required for suppression of astrocyte maturation and induction of angiogenesis. Astrocytic malfunction can lead to impaired retinal vascularization, breakdown of the blood-retinal-barrier and reactive gliosis, contributing to a cohort of blinding diseases such as retinopathy of prematurity (ROP), coloboma, and glaucoma. This project is expected to illuminate the mechanism of PDGF and FGF signaling in astrocytes, which will contribute to understanding and treatment of ocular diseases.

项目概要视网膜星形胶质细胞形成视网膜神经胶质血管网络的组成部分。他们有助于视网膜脉管系统的建立，维持血视网膜屏障和视网膜神经节细胞的健康。尽管已知有一些信号通路是活跃的在星形胶质细胞中，它们如何整合以调节星形胶质细胞的发育和生理学仍然是不太了解。本项目将研究PDGF和FGF的作用和机制信号传导是星形胶质细胞发育中两种密切相关的受体酪氨酸激酶途径。经过生成小鼠突变体并进行活体成像，我们将描绘 PDGF 信号传导星形胶质细胞特有的级联，并了解它如何调节星形胶质细胞的迁移行为星形胶质细胞。此外，我们还将研究FGF信号传导的分子机制。调节星形胶质细胞的成熟。最后，我们将检验 FGF 和 PDGF 信号传导的假设是抑制星形胶质细胞成熟和诱导血管生成所必需的。星形胶质细胞功能障碍可能导致视网膜血管受损、血-视网膜屏障破坏和反应性神经胶质增生，导致一系列致盲疾病，例如视网膜病变早产儿 (ROP)、缺损和青光眼。该项目预计将照亮星形胶质细胞中 PDGF 和 FGF 信号传导机制，这将有助于理解和治疗眼部疾病。