Project description
A holistic view on brain macrophages
Microglia are the most prominent and long-lived innate immune cells in the central nervous system. They emerge early on during development in the yolk sac, and their primary role is to fight off pathogens and remove cellular debris to maintain tissue homeostasis. The aim of the EU-funded MADEFUN project is to delineate how the different types of macrophages in the brain differentiate and impact brain development. Apart from determining their spatiotemporal distribution, researchers will also study the involvement of macrophages in neuropathological conditions such as neurodegeneration and inflammation.
Objective
Macrophages are part of the mononuclear phagocyte system and play critical roles in innate immune responses. They further exert crucial organ-specific functions to warrant tissue homeostasis. Most macrophages are long-lived and derive from embryonic precursors. The central nervous system (CNS) contains several macrophage populations, of which microglia are the most prominent and abundant population residing in the CNS parenchyma. Besides being implicated in CNS pathologies, microglia guide neuronal development, are critical for neurogenesis and contribute to the maintenance of tissue homeostasis. At the interface between the brain and the periphery reside choroid plexus, perivascular and meningeal macrophages (‘border-associated’ macrophages, BAMs). While they mostly also originate from embryonic precursors, the differentiation cues and their specific roles in development and in health and disease are poorly understood. Here we will delineate the spatiotemporal emergence of BAMs and microglia, the impact of the local microenvironment on their phenotype and function, and their role in brain development. We will further analyze the role of BAMs and microglia in physiological and neuropathological conditions (neurodegeneration, CNS infection and inflammation). We have recently described a novel ‘microglia-specific’ conditional mouse and we are currently establishing an inducible system to specifically manipulate BAMs. We will use these to genetically intervene in different cytokine signaling pathways in combination with fate-mapping in vivo. The proposed research project will provide a deeper insight into microglia and BAM biology and their functional specializations at different stages of life.
Fields of science
Keywords
Programme(s)
Funding Scheme
ERC-COG - Consolidator GrantHost institution
8006 Zurich
Switzerland