Wittamer V and Bertrand JY.
Cell Mol Life Sci. 2020
Our research aims at providing novel insights into the basic biology of mononuclear phagocytes, with a focus on microglia, the resident immune cells of the central nervous system. In particular, we are interested in how the microglial network is established during vertebrate development, and subsequently maintained throughout life. Understanding these key aspects of microglia biology are of major importance since microglia are implicated in the pathology of most, if not all neurological disorders, and are now considered as major putative targets for therapeutic intervention in the field of neuroinflammation.
To address these fundamental questions in vivo, we use zebrafish, a model system that offers unique experimental approaches. Indeed, because the first steps of microglia ontogeny occur early during embryogenesis, transparent transgenic zebrafish embryos offer great opportunities to characterize these processes in a non invasive way.
Our program relies on targeted genome editing gene manipulation using the CRISPR/Cas9 technologies to manipulate microglia gene functions in vivo and examine the subsequent effects on microglia biology. We also perform live imaging analyses on fluorescent transgenic embryos to directly observe the behavior of microglial cells in vivo, as they interact in their microenvironment. In the long run, we also plan to develop zebrafish models of neurodegeneration and cancer that should prove instrumental for the analysis of microglia contribution in pathology and disease. Ultimately, our goal is to uncover novel important microglial functions and molecular mechanisms that can be translated to mammals.