Gliotransmission orchestrates neuronal type-specific axon regeneration

作者：Fei Wang, Kendra Takle Ruppell, Songlin Zhou, Yun Qu, Jiaxin Gong, Ye Shang, Yi Li, Yang Xiang · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2019 · DOI：10.1101/799635 · 被引用次数：1 · 研究领域：Neurobiology and Insect Physiology Research、Nerve injury and regeneration、Invertebrate Immune Response Mechanisms

SUMMARY Why closely related neuronal types differ in their axon regenerative abilities remains elusive. Here, we demonstrate gliotransmission determines such a difference in Drosophila larval sensory neurons. Axotomy activates ensheathing glia, which signal to regenerative neurons through the gliotransmitter adenosine, to mount regenerative programs including neuronal activity and Ras. Surprisingly, ensheathing glia do not signal to non-regenerative neurons. Such neuronal type-specific responses to gliotransmission result from specific expression of adenosine receptors in regenerative neurons. Disrupting gliotransmission impedes regeneration of regenerative neurons. Strikingly, reconstitution of gliotransmission in non-regenerative neurons enables them to regenerate. Furthermore, activation of an adenosine receptor ortholog in adult mice promotes both regeneration and survival of retinal ganglion cells, uncovering a conserved pro-regenerative role of adenosine receptors. Our studies demonstrate gliotransmission as a novel mechanism by which glia instruct axon regeneration, with neuronal type-specificity, and suggest targeting purinergic signaling as a new strategy for mammalian central nervous system repair. HIGHLIGHTS Ensheathing glia differentially interact with Drosophila sensory neuron types through gliotransmission Gliotransmission mounts axon regenerative programs in selective neuronal types Neuronal firing pattern but not overall excitability dictates axon regeneration...