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Actin dependent astrocytic infiltration is a key step for axon defasciculation during remodeling

ABSTRACT: A strocytes are essential for synapse formation, maturation and plasticity, yet their function during developmental neuronal remodeling is largely unknown To identify astrocytic molecules required for axon pruning of mushroom body ( γ neurons in Drosophi la we profile d the expression of astrocytes before ( and after ( remodeling. F ocus ing on genes enriched in larval astrocytes we identified 12 genes that are required in astrocytes, for axon pruning including the F actin regulat ors Arpc1 and form3 Interestingly, perturbing astrocytic actin dynamics did not affect their gross morphology migration or TGF β secretion In contrast, actin dynamics was required for astrocyte infiltration into the axon bundle at the onset of pruning. Remarkably, decreasing axonal adhesion facilitated the infiltration of Arpc1 KD astrocytes, and suppressed the pruning defect driven by the astrocytic perturbation 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

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE190743 | GEO | 2023/02/12

REPOSITORIES: GEO

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Project description:Remodeling of the actin cytoskeleton through actin dynamics (assembly and disassembly of filamentous actin) is known to be essential for numerous basic biological processes. In addition, recent in vitro studies provided evidence that actin dynamics participate in the control of gene expression. A spontaneous mouse mutant, corneal disease 1 (corn1), is deficient for a regulator of actin dynamics, destrin (DSTN; also known as actin depolymerizing factor or ADF), and develops epithelial hyperproliferation and neovascularization in the cornea. Dstncorn1 mice exhibit the actin dynamics defect in the corneal epithelial cells as evidenced by increased filamentous actin, offering an in vivo model to investigate the physiological significance of the transcriptional regulation by actin dynamics. To examine the effect of the Dstncorn1 mutation on gene expression, we performed a microarray analysis using the cornea from Dstncorn1 and wild-type control mice. A dramatic alteration of gene expression was observed in the Dstncorn1 cornea, with 1,226 annotated genes differentially expressed. Functional annotation of these genes revealed that most significantly enriched functional categories are associated with actin and/or cytoskeleton. Among genes that belong to these categories, a considerable number of serum response factor (SRF) target genes were found, indicating the existence of the actin-SRF pathway of transcriptional regulation in vivo. A comparative study using an allelic mutant strain, Dstncorn1-2J, with milder corneal phenotypes also suggested that the severity of the actin dynamics defect correlates with the level of gene expression changes. Our study provides evidence that actin dynamics have a strong impact on gene expression in vivo. Experiment Overall Design: Microarray analysis was performed in triplicate with RNA from each genotype, A. BY H2bc H2-T18f/SnJ (A. BY wild-type), A. BY H2bc H2-T18f/SnJ-Dstncorn1/J (Dstncorn1), C57BL/6J (B6 wild-type), C57BL/6JSmn-Dstncorn1-2J/J (Dstncorn1-2J), and C.129S2(B6)-Il8rbtm1Mwm/J (Il8rb-/-), hybridized to three Affymetrix MG 430 2.0 arrays.

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Actin dependent astrocytic infiltration is a key step for axon defasciculation during remodeling

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