Reverse genetic screen reveals that Il34 facilitates yolk sac macrophage distribution and seeding of the brain

Microglia are brain-resident macrophages, which have specialized functions important in brain development and in disease. They colonize the brain in early embryonic stages, but few factors that drive the migration of yolk sac macrophages (YSMs) into the embryonic brain, or regulate their acquisition of specialized properties, are currently known. Here, we present a CRISPR/Cas9-based in vivo reverse genetic screening pipeline to identify new microglia regulators using zebrafish. Zebrafish larvae are particularly suitable due to their external development, transparency and conserved microglia features. We targeted putative microglia regulators, by Cas9/gRNA complex injections, followed by Neutral-Red-based visualization of microglia. Microglia were quantified automatically in 3-day-old larvae using a software tool we called SpotNGlia. We identified that loss of zebrafish colony-stimulating factor 1 receptor (Csf1r) ligand, Il34, caused reduced microglia numbers. Previous studies on the role of IL34 in microglia development in vivo were ambiguous. Our data, and a concurrent paper, show that, in zebrafish, il34 is required during the earliest seeding of the brain by microglia. Our data also indicate that Il34 is required for YSM distribution to other organs. Disruption of the other Csf1r ligand, Csf1, did not reduce microglia numbers in mutants, whereas overexpression increased the number of microglia. This shows that Csf1 can influence microglia numbers, but might not be essential for the early seeding of the brain. In all, we identified il34 as a modifier of microglia colonization, by affecting distribution of YSMs to target organs, validating our reverse genetic screening pipeline in zebrafish.Applied Science

Silentium: DSE 2018: A Silent Delivery Drone

Major delivery companies such as DHL, UPS or Amazon have been developing small drones to deliver packages. This alternative to truck delivery is expected to start operating in the near future. The advantages of it are its speed, price, safety and sustainability: parcels would not be subjected to traffic and they would be delivered within an hour, it is 10% less expensive and it means a 73% reduction in CO2 emissions when compared to truck delivery, as well as a relieve in the road traffic network. The only drawback is that the noise produced by current drones is deemed by humans as more annoying than car noise due to its high frequency. The mission of the Silent Delivery Drone project is to provide a drone delivery system that is faster, less expensive and has lower emissions than truck delivery while complying with Dutch noise regulations. The presented innovative configuration is a combination of a quadcopter, suitable for Vertically Taking-Off and Landing (VTOL) in densely populated regions, and a flying wing, optimized for the cruise phase. It consists of a horizontal propeller used during cruise and four vertical propellers for VTOL. The drone can carry a payload of up to 2.5 kg, which corresponds to 89% of the packages delivered yearly worldwide. Four packages can be delivered while flying the maximum range of 30 km. Thanks to the low required revolutions per minute, the absolute maximum noise caused by the drone is 58 dBA at take-off from 7.5 m and 25 dBA during cruise from a distance of 120 m. This meets the Dutch night noise regulations which stablish a peak noise level of 65 dBA and average noise level of 40 dBA. We believe that a fleet of Silentium drones would revolutionize the way we perceive package delivery and it would mark the next step towards a greener, smarter and more connected future.Aerospace Engineerin