Peter F. Hitchcock, Ph.D.
In the vertebrate retina Müller glia have multiple roles - light guides, support cells and injury-induced stem cells. In the fish retina, when Müller glia function as stem cells, they completely replace dying cells and restore visual function. Following retinal injury, Müller glia re-enter the cell cycle and generate rapidly dividing progenitors that give rise to the regenerated neurons. When the neuronal death is extensive, this regenerative neurogenesis can replace all cell types, whereas, if death is limited to photoreceptors, only photoreceptors are regenerated. Understanding stem cell-based genesis and regeneration of neurons and photoreceptors is the focus of our work, and our goal is to identify the molecular mechanisms that guide stem cells in both the developing an injured retina to generate neurons and photoreceptors.
My lab is presently undertaking three lines of research. The first investigates the function of the transcription factor, NeuroD. Our studies will test the mechanisms by which NeuroD functions during both photoreceptor genesis and regeneration. The second line of research tests our hypothesis that that microglia regulate aspects of neuronal regeneration in the retina. The third line of research investigates the function of the soluble growth factor, midkine-a, which is expressed by stem cells and progenitors during both developmental and regenerative neurogenesis.
These lines of research use the zebrafish as the animal model. The teleost retina is the only vertebrate central nervous tissue where intrinsic stem cells can regenerate a single neuronal type, which is integrated into existing synaptic circuits, or regenerate all cell types, which can fully restore the original tissue. Identifying the cellular and molecular determinants of neuronal genesis and regeneration will yield important results, which will expand our knowledge of intrinsic neural stem and progenitor cells and help identify core requirements for treating retinal injury and disease.