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Project Summary

Microglia represent the primary innate immune effector cell of the CNS and act as sentinels for the detection of pathogen invasion or CNS damage. In healthy brain tissue, they appear as highly branched cells (“ramified” morphology) with pronounced cell protrusions, which are extremely dynamic and survey the surrounding microenvironment for cell debris. Upon brain injury, microglia undergo shape changes to adopt a roundish “amoeboid” morphology, sometimes followed by cell displacement and movement through the tissue. To date, the detailed mechanisms that determine these shape changes and microglia migration in vivo have remained largely unclear. Cell morphology results from the interplay of actin polymerization, actomyosin contraction and cell adhesion, the latter mainly mediated by adhesion receptors of the integrin family. Although it is well known that microglia express several members of the integrin receptor family, their roles for microglia function in vivo have remained unsolved. We will use dynamic in situ imaging in combination with mouse genetics to address the role of integrin function for (a) microglia homeostasis and anatomical positioning within the healthy brain, (b) microglia activation, migration and phagocytosis after CNS damage or inflammation, and (c) the recruitment of bone-marrow-derived progenitors from the blood, their differentiation and movement within the diseased CNS.