PDGF signaling in lens development

PDGF信号在晶状体发育中的作用

基本信息

批准号：
8984996
负责人：
Xin Zhang
金额：
$ 35.32万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-01 至 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8984996
关键词：
Animal Model Apoptosis Apoptotic Binding Biochemical Biological Cell Cycle Cell Differentiation process Cell Line Cell Proliferation Cell Survival Cells Complex Data Defect Development Disease Embryonic Development Epithelial Cells Equilibrium Eye Fibroblast Growth Factor Future Genetic Genetic Programming Genetic screening method Goals Growth Factor Homeostasis Human Human Development Image Impairment In Vitro Investigation Lead Lens Fiber Lens development Ligands MAP Kinase Gene Mediator of activation protein Microphthalmos Modeling Molecular Mutant Strains Mice Outcome Pathway interactions Pattern Phenotype Physiology Platelet-Derived Growth Factor Platelet-Derived Growth Factor Receptor Play Prevention Proto-Oncogene Proteins c-akt Receptor Protein-Tyrosine Kinases Regenerative Medicine Research Rest Role Signal Pathway Signal Transduction Signaling Molecule Stem cells Testing Vision Vision research Visual Accommodation Visual system structure Work base biological systems cellular targeting congenital cataract human FRAP1 protein human disease in vivo inhibitor/antagonist insight lens mouse model mutant notch protein premature programs public health relevance therapeutic development

项目摘要

DESCRIPTION (provided by applicant): Congenital cataract and icrophthalmia are devastating vision diseases that can be caused by aberrant lens development. As the focal point of the visual system, lens is also important for accommodation of the eye to image objects at variable distance. Although many growth factors have been implicated in lens development, how these factors interact to orchestrate the precise developmental program is still poorly understood. As these signaling molecules are also involved in numerous human diseases in the rest of the eye, investigation of these signaling pathways could potentially lead to better understanding and treatment of ocular diseases. In this project, we will focus on the role of PDGF signaling in lens development. By generating animal models in PDGF pathway, we aim to delineate the signaling cascade activated by PDGF within the lens cells. Furthermore, we will define how PDGF and FGF, two closely related growth factors, both cooperate and antagonize during lens development. This will be followed by the investigation of PI3K and Ras signaling interaction in cell proliferation and differentiation. Finally, we will investigate how these signaing pathways impinge on the activity of Notch signaling to regulate the differentiation program of lens progenitor cells. Signaling control of cell proliferation and differentiation is fundamental t development and homeostasis of biological systems. Our study of signaling mechanism may thus have significant impact beyond vision research.

描述（由申请人提供）：先天性白内障和小眼球症是由晶状体发育异常引起的破坏性视力疾病。作为视觉系统的焦点，晶状体对于眼睛在不同距离处成像也很重要。生长因子与晶状体发育有关，但人们对这些因子如何相互作用以协调精确的发育程序仍知之甚少，因为这些信号分子也与眼睛其他部位的许多人类疾病有关，因此对这些信号通路的研究。在这个项目中，我们将重点研究 PDGF 信号在晶状体发育中的作用，通过建立 PDGF 通路的动物模型，我们的目标是描述 PDGF 在晶状体内激活的信号级联。此外，我们将定义 PDGF 和 FGF 这两种密切相关的生长因子在晶状体发育过程中如何协同和拮抗，随后将研究 PI3K 和 Ras 信号传导在细胞增殖和分化中的相互作用。如何这些信号传导途径影响Notch信号传导的活性，以调节晶状体祖细胞的分化程序。细胞增殖和分化的信号传导控制是生物系统的基本发育和稳态，因此我们对信号传导机制的研究可能具有超越视觉研究的重大影响。