Deciphering molecular recruitment mechanisms of microglial progenitors during development

Juniorprof. Dr. Katrin Kierdorf

• A09N

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.