Project Summary

Microglia progenitors arise from the yolk sac during embryonic development and colonize the central
nervous system (CNS) at 9.5 days post conception (dpc). During development, they further expand and
differentiate until the microglial network is fully established in the adult. Recent studies have linked defects
in microglial development to neurodegenerative and neuropsychiatric diseases. However, detailed
molecular mechanisms of microglial recruitment during development are still ill-defined and poorly understood.
With this project proposal, we aim to identify and characterize molecular recruitment mechanisms
of microglia during development. First, we will utilise unbiased transcriptomic and proteomic approaches
to screen and identify potential recruitment signals from the developing CNS. Identified candidate genes
will be further explored for their specific role in microglial recruitment. Second, we will focus on integrins
during microglial progenitor recruitment, which we already identified as potential adhesion molecules for
microglial colonization of the CNS. Here we will employ integrin-deficient genetic mouse models along
with pharmaceutical inhibition of integrin signalling to elucidate how different integrins affect the recruitment
of microglial progenitors. Finally, we will investigate if the recruitment signals for microglial progenitors
to the CNS are tissue-specific. In summary, these data will allow us to obtain a detailed understanding
of the molecular machinery used by microglial progenitors to efficiently colonize the CNS and if these
factors are unique for microglial progenitors.