PDGF signaling in lens development

点击翻译按钮获取中文摘要

 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.