Abstract
Synaptic structure and activity are sensitive to environmental alterations. Modulation of synaptic morphology and function is often induced by signals from glia. However, the process by which glia mediate synaptic responses to environmental perturbations such as hypoxia remains unknown. Here, we report that, in the mutant for Trachealess (Trh), the Drosophila homolog for NPAS1 and NPAS3, smaller synaptic boutons form clusters named satellite boutons appear at larval neuromuscular junctions (NMJs), which is induced by the reduction of internal oxygen levels due to defective tracheal branches. Thus, the satellite bouton phenotype in the trh mutant is suppressed by hyperoxia, and recapitulated in wild-type larvae raised under hypoxia. We further show that hypoxia-inducible factor (HIF)-1α/Similar (Sima) is critical in mediating hypoxia-induced satellite bouton formation. Sima upregulates the level of the Wnt/Wingless (Wg) signal in glia, leading to reorganized microtubule structures within presynaptic sites. Finally, hypoxia-induced satellite boutons maintain normal synaptic transmission at the NMJs, which is crucial for coordinated larval locomotion.
Highlights
Animals need oxygen and food, to sustain life, and for motility
We assess the morphology of Drosophila neuromuscular junctions (NMJs), a model system to study development and function of synapses, in two hypoxia conditions, one with raising wild-type larvae in hypoxia, and the other in the trachealess mutant in which the trachea is defective, causing insufficient oxygen supply
We further show that glial cells respond to hypoxia by elevating Wnt/Wg expression to mediate synaptic bouton reorganization through HIF1-α/Sima in Drosophila
Summary
Animals need oxygen and food, to sustain life, and for motility. In vertebrates, oxygen and nutrients are delivered through the vascular systems to organs and tissues throughout the body. Nerves and vessels, form close associations and are in physical contact through the third player astrocytes to form neurovascular units (NVU) [2]. Such organization is essential for controlling oxygen and glucose delivery through the blood vessels by neuronal activity, and this regulatory process is mediated through the coupled astrocytes [3]. Oxygen is supplied by ambient diffusion to inner cells [5] Insects such as Drosophila have evolved a prototype of the tracheal system to deliver oxygen and a primitive vascular system, the dorsal vessel, to facilitate nutrient delivery [6]. The physical association of nerves, trachea, and glial processes has been demonstrated at the NMJs of adult Drosophila flight muscles [7]
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