Glial Draper signaling triggers cross-neuron plasticity in bystander neurons after neuronal cell death in Drosophila

Neuronal cell death and subsequent brain dysfunction are hallmarks of aging and neurodegeneration, but how the nearby healthy neurons (bystanders) respond to the death of their neighbors is not fully understood. In the Drosophila larval neuromuscular system, bystander motor neurons can structurally and functionally compensate for the loss of their neighbors by increasing their terminal bouton number and activity. We term this compensation as cross-neuron plasticity, and in this study, we demonstrate that the Drosophila engulfment receptor, Draper, and the associated kinase, Shark, are required for cross-neuron plasticity. Overexpression of the Draper-I isoform boosts cross-neuron plasticity, implying that the strength of plasticity correlates with Draper signaling. In addition, we find that functional cross-neuron plasticity can be induced at different developmental stages. Our work uncovers a role for Draper signaling in cross-neuron plasticity and provides insights into how healthy bystander neurons respond to the loss of their neighboring neurons. Neuronal death is a feature of development and neurodegeneration. Here, the authors report that ablation of Drosophila motor neurons triggers Draper-dependent signaling in glia to engage 'cross-neuron plasticity' in bystander neurons.

Automated summary

Neuronal death and brain dysfunction are characteristics of aging and neurodegeneration. This study demonstrates that healthy neurons can compensate for the death of their neighbors through cross-neuron plasticity in the Drosophila larval neuromuscular system. The Draper engulfment receptor and the Shark kinase are found to be essential for this compensation, and overexpression of the Draper-I isoform enhances cross-neuron plasticity. These findings provide insights into how healthy bystander neurons respond to the loss of neighboring neurons.