Glia Preserve Their Own Functions While Compensating for Neighboring Glial Cell Dysfunction

Glial cells are essential for nervous system development, homeostasis, and disease response, engaging in close interactions with neurons and other glial cells to carry out their functions. A large focus of glial studies has been on investigating how these cells work with neurons to execute their supportive roles, yet glial-glial interactions are even less well understood. Our previous work established that the loss of the secreted neurotrophin, Spätzle 3 (Spz3), from Drosophila cortex glia (CG) results in the morphological degradation of CG during mid to late larval development, where they lose their intricate interactions with neurons and other glial subtypes. Building on this work, we found that the loss of CG-neuron interactions triggers aberrant infiltration and functional compensation from all neighboring glial cell types-astrocytes, ensheathing glia (EG), and subperineurial glia (SPG)-and that both the CG disruption and surrounding aberrant glial extensions are inhibited by blocking CNS growth. These aberrant glial processes are able to compensate for at least one major CG function, the clearance of apoptotic neuronal corpses via Draper-mediated engulfment. Remarkably, even as astrocytes, EG, and SPG divert their cellular resources to extend into new territories and take on new functions, they continue to maintain their normal homeostatic roles such as synaptic remodeling (astrocytes), post-injury clearance of neurite debris (ensheathing glia), and regulation of the blood-brain barrier (SPG). These findings reveal that multiple glial subtypes can dynamically respond to nearby glial dysfunction to preserve CNS homeostasis, highlighting the resilience and adaptability of glia across subtypes.