The asymmetric brain: Utilizing hyper-gravity to manipulate developmental symmetries

The evolution and development of all organisms on earth relies on near-constant gravity. Experimental manipulations can create developmental conditions that have never been encountered during evolution, yet reveal developmental mechanisms based on informative phenotypic outcomes; classically, such experiments include transplantation of developing organs as well as pushing boundaries of environmental conditions.Here, we explore the outcome of Drosophila melanogaster brain development at hyper-gravity 10^2 to 10^3 times greater than conventional gravity on earth. Remarkably, Drosophila pupae fully develop when exposed to 300g throughout the period of brain wiring (P50 - P100). The adult brains of such flies exhibit an asymmetric phenotype: synaptic neuropils exhibit a reduction in volume only on the side pointed to by the gravity vector, while the other side appears morphologically normal. Analysis of single cell morphology revealed largely unaltered neuronal branching patterns. However, the investigation of synaptic connectivity with the trans-synaptic tracer trans-tango, revealed a surprisingly dramatic change of synaptic partners to R7 photoreceptor neurons; these changes include a substantial loss of synapses with the main postsynaptic partner Dm8, despite largely unaltered neuronal morphologies. Since the control side of the brain had experienced the same hyper-gravity, yet exhibited normal connectivity, we conclude that hyper-gravity does not directly affect molecular or sub-cellular processes, but caused these effects by a redistribution of resources in the fly pupa.The extent and nature of these synaptic changes reveal the plasticity and principles of how the genetically encoded developmental program leads to specific connectivity during brain wiring.