Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel; Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot 7610001, Israel.
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
Cell Rep. 2023 Feb 28;42(2):112117. doi: 10.1016/j.celrep.2023.112117. Epub 2023 Feb 14.
Astrocytes are essential for synapse formation, maturation, and plasticity; however, their function during developmental neuronal remodeling is largely unknown. To identify astrocytic molecules required for axon pruning of mushroom body (MB) γ neurons in Drosophila, we profiled astrocytes before (larva) and after (adult) remodeling. Focusing on genes enriched in larval astrocytes, we identified 12 astrocytic genes that are required for axon pruning, including the F-actin regulators Actin-related protein 2/3 complex, subunit 1 (Arpc1) and formin3 (form3). Interestingly, perturbing astrocytic actin dynamics does not affect their gross morphology, migration, or transforming growth factor β (TGF-β) secretion. In contrast, actin dynamics is required for astrocyte infiltration into the axon bundle at the onset of pruning. Remarkably, decreasing axonal adhesion facilitates infiltration by Arpc1 knockdown (KD) astrocytes and promotes axon pruning. Conversely, increased axonal adhesion reduces lobe infiltration by wild-type (WT) astrocytes. Together, our findings suggest that actin-dependent astrocytic infiltration is a key step in axon pruning, thus promoting our understanding of neuron-glia interactions during remodeling.
星形胶质细胞对于突触的形成、成熟和可塑性至关重要；然而，它们在发育过程中神经元重塑期间的功能在很大程度上尚不清楚。为了鉴定在果蝇蘑菇体（MB）γ神经元轴突修剪过程中所需的星形胶质细胞分子，我们在重塑之前（幼虫）和之后（成虫）对星形胶质细胞进行了分析。我们专注于在幼虫星形胶质细胞中富集的基因，鉴定出 12 个对于轴突修剪必不可少的星形胶质细胞基因，包括 F-肌动蛋白相关蛋白 2/3 复合物亚基 1（Arpc1）和formin3（form3）。有趣的是，扰乱星形胶质细胞肌动蛋白动力学不会影响它们的总体形态、迁移或转化生长因子β（TGF-β）分泌。相比之下，在修剪开始时，肌动蛋白动力学对于星形胶质细胞浸润到轴突束中是必需的。值得注意的是，减少轴突黏附力有利于 Arpc1 敲低（KD）星形胶质细胞的浸润，并促进轴突修剪。相反，增加轴突黏附力会减少野生型（WT）星形胶质细胞对叶的浸润。总之，我们的研究结果表明，依赖肌动蛋白的星形胶质细胞浸润是轴突修剪的关键步骤，从而促进了我们对重塑过程中神经元-胶质细胞相互作用的理解。
