PDGF signaling in lens development

PDGF信号在晶状体发育中的作用

• 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
• 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

 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.