Dataset Information

1Arp2/3 complex controls microglial cell dynamics and homeostasis by regulating TGF-β signaling.

ABSTRACT: Microglia are the major brain-resident immune cell subsetthat areessential during pathology and physiology in the central nervous system. The regulation of functional elementsrequired for microglialhomeostasis needsto be precisely orchestrated.To date, the underlying mechanismshave not been fully investigated. Here,we show that actin network dynamics mediated by the Arp2/3 complex play a crucial role in microglial cell function. Upon interruption of Arp2/3 complex integrity in the conditional knockoutmouse model, we found significant alterations in microglial cell morphology, motility, and chemotaxisfunction.Transcriptomics analysis revealedthat Arp2/3-deficient microglia downregulatehomeostatic signature and upregulatecell activationthat isassociated with APOE induction, Ms4a7upregulation,and TGFsignaling impairment. In vitrostudies confirm that the Arp2/3 downstream actin-related molecules are required for mediating the TGFsignaling pathway in microglia. Our resultsshow that the Arp2/3complexis required for microglia cell dynamics and plays a key role in maintaining microglial cell homeostasis by regulating the TGF-β signaling.

ORGANISM(S): Mus musculus

PROVIDER: GSE288625 | GEO | 2026/01/31

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Microglia colonize the brain parenchyma at early stages of development and accumulate in specific regions where they actively participate in cell death, angiogenesis, neurogenesis and synapse elimination. A recurring feature of embryonic microglial distribution is their association with developing axon tracts which, together with in vitro data, supports the idea of a physiological role for microglia in neurite development. Yet the demonstration of this role of microglia is still lacking. Here, we have studied the consequences of microglial dysfunction on the formation of the corpus callosum, the largest connective structure in the mammalian brain, which shows consistent microglial accumulation during development. We studied two models of microglial dysfunction: the loss-of-function of DAP12, a key microglial-specific signaling molecule, and a model of maternal inflammation by peritoneal injection of LPS at E15.5. We performed transcriptional profiling of maternally inflamed and Dap12-mutant microglia at E17.5. We found that both treatments principally down-regulated genes involved in nervous system development and function, particularly in neurite formation. We then analyzed the functional consequences of these microglial dysfunctions on the formation of the corpus callosum. We also took advantage of the Pu.1-/- mouse line, which is devoid of microglia. We now show that all three models of altered microglial activity resulted in the same defasciculation phenotype. Our study demonstrates that microglia are actively involved in the fasciculation of corpus callosum axons. To investigate possible roles for microglial during brain development, we challenged microglial function by two complementary approaches. First, we induced maternal inflammation by peritoneal injection of LPS into pregnant dams. Next, we analyzed the consequences of a loss of function of DAP12, a signaling molecule specifically expressed in microglia that is crucial for several aspects of microglia biology (references in Wakselman et al., 2008). We compared the gene expression profiles of microglia from control, maternally-inflamed by LPS (MI), and Dap12-mutated embryos. We isolated RNA from FACS sorted maternally inflamed (by LPS) and Dap12-mutant microglia at E17.5 pooled per pregnant dam; as a control we included PBS treated and untreated (UT) microglia. We compared gene expression between maternally inflamed microlgia (PBSvsLPS) and DAP12-mutant microglia (UTvsDAP12KO).

Dataset Information

1Arp2/3 complex controls microglial cell dynamics and homeostasis by regulating TGF-β signaling.

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets