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.
Despite of the critical importance of PDGF signaling in physiology and development, very little is known about the role of PDGF in lens development. This study will examine how PDGF activates cellular targets and interacts with other signaling pathway within the lens. Lens development and homeostasis is essential for the function of the visual system. Clarification of PDGF signaling network will enhance our understanding of congenital ocular diseases and guide future efforts in therapeutic development.
| Cvekl, Ales; Zhang, Xin (2017) Signaling and Gene Regulatory Networks in Mammalian Lens Development. Trends Genet 33:677-702 |
| Mathew, Grinu; Hannan, Abdul; Hertzler-Schaefer, Kristina et al. (2016) Targeting of Ras-mediated FGF signaling suppresses Pten-deficient skin tumor. Proc Natl Acad Sci U S A 113:13156-13161 |
| Tao, Chenqi; Zhang, Xin (2016) Retinal Proteoglycans Act as Cellular Receptors for Basement Membrane Assembly to Control Astrocyte Migration and Angiogenesis. Cell Rep 17:1832-1844 |
| Balasubramanian, Revathi; Zhang, Xin (2016) Mechanisms of FGF gradient formation during embryogenesis. Semin Cell Dev Biol 53:94-100 |
