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Published on: August 3, 2018
Microglia-Specific Expression of Olfml3 Is Directly Regulated by Transforming Growth Factor β1-Induced Smad2
Nicolas Neidert1, Alexander von Ehr1, Tanja Zöller1
1Department of Molecular Embryology, Faculty of Medicine, Institute for Anatomy and Cell Biology, University of Freiburg, Freiburg, Germany.
Abstract:
Microglia maturation takes place during the postnatal weeks and is characterized by the establishment of a unique microglia-specific gene expression pattern. Tmem119, Fcrls, Hexb, and Olfml3 have been identified among these microglia-specific genes. Transforming growth factor β1 (TGFβ1) has been reported as a critical factor for microglia maturation and maintenance and active TGFβ signaling precedes the inductions of microglial gene expression. In this study, we demonstrate Olfml3 expression in adult microglia and further provide evidence that TGFβ1 induces upregulation of Olfml3 expression in postnatal microglia. Using chromatin immunoprecipitation and microglia-specific silencing of TGFβ signaling in vitro and in vivo, we in clearly show that Olfml3 is a direct TGFβ1/Smad2 target gene. Together, our data underline the importance of TGFβ1 as a critical regulator of microglia functions and microglia maturation and further broaden our understanding of TGFβ1-mediated effects on the resident immune cells of the central nervous system.
Insights
Transforming growth factor beta 1 (TGFβ1) is crucial for microglia maturation. This study shows TGFβ1 directly upregulates Olfactory 3 (Olfml3) expression, a key microglia-specific gene.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia maturation involves establishing unique gene expression patterns during postnatal development.
- Transforming growth factor beta 1 (TGFβ1) is a critical regulator of microglia maturation and maintenance.
- Active TGFβ signaling precedes the induction of microglial gene expression.
Purpose of the Study:
- To investigate the role of TGFβ1 in regulating Olfactory 3 (Olfml3) expression in microglia.
- To confirm Olfml3 as a direct target gene of TGFβ1 signaling.
Main Methods:
- Chromatin immunoprecipitation assays were used to assess gene regulation.
- Microglia-specific silencing of TGFβ signaling was performed both in vitro and in vivo.
- Gene expression analysis was conducted to evaluate the impact of TGFβ1 signaling.
Main Results:
- Olfml3 expression was confirmed in adult microglia.
- TGFβ1 was shown to induce the upregulation of Olfml3 expression in postnatal microglia.
- Olfml3 was identified as a direct TGFβ1/Smad2 target gene.
Conclusions:
- TGFβ1 is a critical regulator of microglia functions and maturation.
- The findings deepen the understanding of TGFβ1-mediated effects on central nervous system resident immune cells.
- Olfml3 is a key gene regulated by TGFβ1 during microglia development.
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