Abstract
The remodeling of neurons is a conserved fundamental mechanism underlying nervous system maturation and function. Astrocytes can clear neuronal debris and they have an active role in neuronal remodeling. Developmental axon pruning of Drosophila memory center neurons occurs via a degenerative process mediated by infiltrating astrocytes. However, how astrocytes are recruited to the axons during brain development is unclear. Using an unbiased screen, we identify the gene requirement of orion, encoding for a chemokine-like protein, in the developing mushroom bodies. Functional analysis shows that Orion is necessary for both axonal pruning and removal of axonal debris. Orion performs its functions extracellularly and bears some features common to chemokines, a family of chemoattractant cytokines. We propose that Orion is a neuronal signal that elicits astrocyte infiltration and astrocyte-driven axonal engulfment required during neuronal remodeling in the Drosophila developing brain.
Highlights
The remodeling of neurons is a conserved fundamental mechanism underlying nervous system maturation and function
Altering the ecdysone signaling in astrocytes, during metamorphosis, results both in a partial axon pruning defect, visualized as either some individual larval axons or as thin bundles of intact larval axons remaining in the adults, and in a strong defect in clearance of debris, visualized by the presence of clusters of axonal debris
We show that Orion is secreted from the neurons, remains near the axon membranes where it associates with infiltrating astrocytes, and is necessary for astrocyte infiltration into the γ bundle
Summary
The remodeling of neurons is a conserved fundamental mechanism underlying nervous system maturation and function. Produced unpruned axons similar to that in orion[1], the debris is not apparent likely due to an incomplete inactivation of the gene expression by the RNAi (Fig. 1l and Supplementary Fig. 5d).
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