PUBLICATION
miR-124 contributes to the functional maturity of microglia
- Authors
- Svahn, A.J., Giacomotto, J., Graeber, M.B., Rinkwitz, S., Becker, T.S.
- ID
- ZDB-PUB-150718-2
- Date
- 2016
- Source
- Developmental Neurobiology 76(5): 507-18 (Journal)
- Registered Authors
- Becker, Thomas S., Giacomotto, Jean, Rinkwitz, Silke, Svahn, Adam
- Keywords
- Chemotaxis, Development, Microglia, Phagocytosis, miRNA
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Apoptosis/physiology
- Cell Movement/physiology
- Cell Survival/physiology
- Gene Knockdown Techniques
- Macrophages/metabolism
- Membrane Proteins/metabolism
- MicroRNAs/genetics
- MicroRNAs/metabolism*
- Microglia/metabolism*
- Neurons/metabolism
- Phagocytosis/physiology
- Sequence Homology
- Superior Colliculi/metabolism
- Zebrafish
- Zebrafish Proteins/metabolism
- PubMed
- 26184457 Full text @ Dev. Neurobiol.
Citation
Svahn, A.J., Giacomotto, J., Graeber, M.B., Rinkwitz, S., Becker, T.S. (2016) miR-124 contributes to the functional maturity of microglia. Developmental Neurobiology. 76(5):507-18.
Abstract
During early development of the central nervous system (CNS), a subset of yolk-sac derived myeloid cells populate the brain and provide the seed for the microglial cell population, which will self-renew throughout life. As development progresses, individual microglial cells transition from a phagocytic amoeboid state through a transitional morphing phase into the sessile, ramified and normally non-phagocytic microglia observed in the adult CNS under healthy conditions. The molecular drivers of this tissue-specific maturation profile are not known. However, a survey of tissue resident macrophages identified miR-124 to be expressed in microglia. In this study we used transgenic zebrafish to over-express miR-124 in the mpeg1 expressing yolk-sac-derived myeloid cells that seed the microglia. In addition, a systemic sponge designed to neutralize the effects of miR-124 was used to assess microglial development in a miR-124 loss-of-function environment. Following the induction of miR-124 overexpression, microglial motility and phagocytosis of apoptotic cells were significantly reduced. miR-124 overexpression in microglia resulted in the accumulation of residual apoptotic cell bodies in the optic tectum, which could not be achieved by miR-124 overexpression in differentiated neurons. Conversely, expression of the miR-124 sponge caused an increase in the motility of microglia and transiently rescued motility and phagocytosis functions when activated simultaneously with miR-124 overexpression. This study provides in vivo evidence that miR-124 activity has a key role in the development of functionally mature microglia. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping