miR-124 Contributes to the functional maturity of microglia

Svahn, Adam J., Giacomotto, Jean, Graeber, Manuel B., Rinkwitz, Silke and Becker, Thomas S. (2015) miR-124 Contributes to the functional maturity of microglia. Developmental Neurobiology, 1-12. doi:10.1002/dneu.22328


Author Svahn, Adam J.
Giacomotto, Jean
Graeber, Manuel B.
Rinkwitz, Silke
Becker, Thomas S.
Title miR-124 Contributes to the functional maturity of microglia
Formatted title
miR-124 Contributes to the functional maturity of microglia
Journal name Developmental Neurobiology   Check publisher's open access policy
ISSN 1932-846X
1932-8451
Publication date 2015-07-01
Sub-type Article (original research)
DOI 10.1002/dneu.22328
Open Access Status Not Open Access
Start page 1
End page 12
Total pages 12
Place of publication Hoboken, United States
Publisher John Wiley and Sons
Formatted 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 nonphagocytic 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 overexpress 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.
Keyword Chemotaxis
Development
Microglia
MiRNA
Phagocytosis
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
Queensland Brain Institute Publications
 
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Created: Sun, 31 Jan 2016, 20:20:49 EST by Jean Giacomotto on behalf of Learning and Research Services (UQ Library)