Research Interests
The main interest of our lab is to understand the molecular and cellular mechanisms underlying development of the vertebrate central nervous system. We use the mouse and chicken retinas as models to study cell fate specification of neural progenitors during development. In addition, we study the maintenance and activation of the adult retinal stem cell niche under conditions that cause retinal degeneration. The mature retina is composed of seven major cell types that are generated from multipotent neural progenitors during neurogenesis. The cell fate choices of uncommitted neural progenitor cells are influenced by both cell-extrinsic cues and cell-intrinsic determinants. We are particularly interested in how extracellular signaling molecules regulate progenitor behaviors through key transcription factors that specify various retinal cell types. Our current studies center around several signaling molecules, including Sonic hedgehog (Shh), vascular endothelial growth factor (VEGF), and ciliary neurotrophic factor (CNTF). Functions of these signaling pathways in retinogenesis are investigated using molecular genetic approaches through tissue-specific gene knockout and knockdown, as well as viral and non-viral gene misexpression. The cell type-specific responses to different extracellular signals are analyzed at cellular and transcriptional levels both in vivo and in primary neuronal culture systems. The goal of these studies is to elucidate how neural progenitor cells integrate and respond to multiple environmental signals during formation of the light sensing retinal neural network. In addition to molecular mechanisms involved in normal neural development, we are investigating cell-cell signaling in the presumptive adult retinal stem cell niche. The roles of various signaling pathways in maintenance and activation of the intrinsic stem cell pool are addressed by molecular genetic analyses in vivo and also tested in neural stem cell cultures in vitro. The potential of signaling molecules in triggering endogenous stem cell amplification is also studied by viral vector-mediated gene delivery. Results from these investigations will enhance our abilities to harness the potential of neural stem cells as therapeutic tools in combating retinal degeneration.