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：
9111908
负责人：
Xin Zhang
金额：
$ 35.3万
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/9111908
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 FRAP1 gene Fibroblast Growth Factor Future Genetic Genetic Programming Genetic screening method Goals Growth Health Homeostasis Human Human Development Image 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 impairment Visual system structure Work base biological systems cellular targeting congenital cataract human disease in vivo inhibitor/antagonist insight lens mouse model mutant notch protein premature programs therapeutic development

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 FRAP1 gene Fibroblast Growth Factor Future Genetic Genetic Programming Genetic screening method Goals Growth Health Homeostasis Human Human Development Image 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 impairment Visual system structure Work base biological systems cellular targeting congenital cataract human disease in vivo inhibitor/antagonist insight lens mouse model mutant notch protein premature programs therapeutic development

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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（由适用提供）：先天性白内障和iTrophthalmia是毁灭性的视力疾病，可能是由异常的晶状体发育引起的。作为视觉系统的焦点，镜头对于在可变距离处的图像对象适应对象也很重要。尽管在晶状体开发中已经实施了许多增长因素，但这些因素如何相互作用以策划确切的发展计划的相互作用仍然很少了解。由于这些信号分子在其余眼中也参与了许多人类疾病，因此对这些信号通路的研究可能会导致更好地理解和治疗眼部疾病。在这个项目中，我们将重点关注PDGF信号在镜头开发中的作用。通过在PDGF途径中产生动物模型，我们的目标是描述透镜细胞中PDGF激活的信号传导级联反应。此外，我们将定义PDGF和FGF的两个最后，我们将如何研究这些签名途径如何影响Notch信号的活性以调节透镜祖细胞的分化程序。细胞增殖和分化的信号控制是生物系统的基本发展和稳态。因此，我们对信号机制的研究可能会在视力研究之外产生重大影响。