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轴突趋化因子样 Orion 在蘑菇体神经元重塑过程中诱导星形胶质细胞浸润和吞噬。

Axonal chemokine-like Orion induces astrocyte infiltration and engulfment during mushroom body neuronal remodeling.

机构信息

IGH, Centre National de la Recherche Scientifique, Univ Montpellier, Montpellier, France.

Dr. John T. Macdonald Foundation Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.

出版信息

Nat Commun. 2021 Mar 23;12(1):1849. doi: 10.1038/s41467-021-22054-x.

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.

摘要

神经元的重塑是神经系统成熟和功能的基础机制之一。星形胶质细胞可以清除神经元碎片,在神经元重塑中发挥积极作用。果蝇记忆中心神经元的发育性轴突修剪是通过浸润星形胶质细胞介导的退行性过程发生的。然而,星形胶质细胞在大脑发育过程中是如何被招募到轴突上的尚不清楚。我们使用一种无偏的筛选方法,鉴定了蘑菇体发育过程中,编码趋化因子样蛋白的基因 orion 的基因需求。功能分析表明,Orion 对于轴突修剪和清除轴突碎片都是必需的。Orion 在细胞外发挥作用,具有趋化因子家族趋化细胞因子的一些共同特征。我们提出,Orion 是一种神经元信号,它引发星形胶质细胞浸润和星形胶质细胞驱动的轴突吞噬,这是果蝇发育大脑中神经元重塑所必需的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eb3/7988174/77add528dd1b/41467_2021_22054_Fig1_HTML.jpg

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