Development and homeostasis of the central nervous system.
Primitive macrophage populations invade the developing vertebrate central nervous system during early embryogenesis, where they differentiate into primitive microglia. The zebrafish allows us to image these primitive microglia in developing tissue in vivo in real-time, allowing us to ask, and answer, questions about microglial functions required for development and homeostasis of healthy tissue.
Degeneration and disease pathology.
How do microglia contribute to, or limit, pathology in the presence of neural tissue degeneration? Do alterations in microglial phenotype impact the outcomes of neuronal degeneration? Can we identify key pathways involved, which can then be considered for therapuetic targets?
Regeneration of retinal tissue.
Zebrafish have a remarkable capacity to regenerate their central nervous system, while mammals do not. Why? Microglia are present in both types of animals, but whether microglia contribute to regenerative vs. pathological outcomes is not clear. The retina provides an excellent tissue to study regeneration of the central nervous system, due to highly stereotypical organization and strong evidence indicating that the Muller glia act as the source of regenerated neurons. This provides an excellent context to determine microglial functions in regeneration of CNS tissue. We can then apply this knowledge to mitigating pathological responses in mammals.
We also collaborate with the Stenkamp lab, here at the University of Idaho. These projects focus on the development, patterning, and regeneration of neurons in the vertebrate retina.