RRC ID 59159
Author Chen PY, Tsai YW, Cheng YJ, Giangrande A, Chien CT.
Title Glial response to hypoxia in mutants of NPAS1/3 homolog Trachealess through Wg signaling to modulate synaptic bouton organization.
Journal PLoS Genet
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.
Volume 15(8)
Pages e1007980
Published 2019-8-1
DOI 10.1371/journal.pgen.1007980
PMID 31381576
PMC PMC6695205
MeSH Animals Animals, Genetically Modified Cell Hypoxia / genetics* DNA-Binding Proteins / metabolism* Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / physiology Gene Expression Regulation, Developmental Gene Knockdown Techniques Intravital Microscopy Larva / physiology Locomotion / genetics Microscopy, Confocal Microtubules / metabolism Models, Animal Neuroglia / cytology Neuroglia / metabolism Neuromuscular Junction / growth & development* Neuromuscular Junction / metabolism Presynaptic Terminals / metabolism Signal Transduction / genetics Synaptic Transmission / physiology* Transcription Factors / genetics Transcription Factors / metabolism* Up-Regulation Wnt1 Protein / metabolism
IF 5.175
Times Cited 1
Drosophila DGRC#105188