PDGF signaling in lens development

 描述（由申请人提供）：先天性白内障和小眼症是破坏性视力疾病，可由异常透镜发育引起。作为视觉系统的焦点，透镜对于眼睛的调节以在可变距离处成像物体也是重要的。虽然许多生长因子与透镜的发育有关，但这些因子如何相互作用以协调精确的发育程序仍然知之甚少。由于这些信号分子也参与了眼睛其他部位的许多人类疾病，因此对这些信号通路的研究可能会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信号在透镜发育中的作用。通过建立PDGF通路的动物模型，我们的目的是描绘由PDGF激活的信号级联在透镜细胞内。此外，我们将确定如何PDGF和FGF，两个密切相关的生长因子，既合作和拮抗透镜的发展。随后将研究PI3K和Ras信号在细胞增殖和分化中的相互作用。最后，我们将研究这些信号通路如何影响Notch信号通路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调控是生物系统发育和稳态的基础。因此，我们对信号传导机制的研究可能会对视觉研究产生重大影响。

 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.