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Beat-Va神经元中星形胶质细胞依赖性的局部神经突修剪

Astrocyte-dependent local neurite pruning in Beat-Va neurons.

作者信息

Lehmann Katherine S, Hupp Madison T, Abalde-Atristain Leire, Jefferson Amanda, Cheng Ya-Chen, Sheehan Amy E, Kang Yunsik, Freeman Marc R

机构信息

Vollum Institute, Oregon Health & Science University , Portland, OR, USA.

Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, CO, USA.

出版信息

J Cell Biol. 2025 Jan 6;224(1). doi: 10.1083/jcb.202312043. Epub 2024 Dec 9.

Abstract

Developmental neuronal remodeling is extensive and mechanistically diverse across the nervous system. We sought to identify Drosophila pupal neurons that underwent mechanistically new types of neuronal remodeling and describe remodeling Beat-VaM and Beat-VaL neurons. We show that Beat-VaM neurons produce highly branched neurites in the CNS during larval stages that undergo extensive local pruning. Surprisingly, although the ecdysone receptor (EcR) is essential for pruning in all other cell types studied, Beat-VaM neurons remodel their branches extensively despite cell autonomous blockade EcR or caspase signaling. Proper execution of local remodeling in Beat-VaM neurons instead depends on extrinsic signaling from astrocytes converging with intrinsic and less dominant EcR-regulated mechanisms. In contrast, Beat-VaL neurons undergo steroid hormone-dependent, apoptotic cell death, which we show relies on the segment-specific expression of the Hox gene Abd-B. Our work provides new cell types in which to study neuronal remodeling, highlights an important role for astrocytes in activating local pruning in Drosophila independent of steroid signaling, and defines a Hox gene-mediated mechanism for segment-specific cell elimination.

摘要

发育性神经元重塑在整个神经系统中广泛存在且机制多样。我们试图鉴定经历了机制上新型神经元重塑的果蝇蛹神经元,并描述重塑的Beat-VaM和Beat-VaL神经元。我们发现,Beat-VaM神经元在幼虫阶段的中枢神经系统中产生高度分支的神经突,这些神经突会经历广泛的局部修剪。令人惊讶的是,尽管蜕皮激素受体(EcR)对所有其他研究的细胞类型的修剪至关重要,但Beat-VaM神经元尽管存在细胞自主阻断EcR或半胱天冬酶信号,仍能广泛重塑其分支。Beat-VaM神经元局部重塑的正确执行反而依赖于星形胶质细胞的外在信号与内在的、不太占主导地位的EcR调节机制相结合。相比之下,Beat-VaL神经元会经历类固醇激素依赖性的凋亡细胞死亡,我们发现这依赖于Hox基因Abd-B的节段特异性表达。我们的工作提供了新的细胞类型来研究神经元重塑,突出了星形胶质细胞在果蝇中独立于类固醇信号激活局部修剪的重要作用,并定义了一种Hox基因介导的节段特异性细胞消除机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/442b/11627112/55d09d782068/jcb_202312043_fig1.jpg

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