Postnatal maturation of microglia is associated with alternative activation and activated TGFβ signaling

Abdelraheim Attaai1,2,3, Nicolas Neidert1, Alexander von Ehr1

  • 1Institute for Anatomy and Cell Biology, Department of Molecular Embryology, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Glia
|March 26, 2018
PubMed

Insights

Transforming growth factor beta 1 (Tgfβ1) is crucial for postnatal microglia maturation. Neuron-derived Tgfβ1 signaling drives microglia maturation and establishes specific gene expression patterns, highlighting its role in brain development and maintenance.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglia, the brain's immune cells, are vital for physiological and pathological processes, including neurodevelopment.
  • Postnatal microglia maturation involves establishing unique gene expression profiles, but the underlying mechanisms are not fully understood.
  • Transforming growth factor beta 1 (Tgfβ1) is hypothesized to be a key mediator in microglia maturation.

Purpose of the Study:

  • To investigate the role of Tgfβ1 signaling in early postnatal microglia maturation.
  • To elucidate the source of Tgfβ1 and its communication with microglia.
  • To identify Tgfβ1-regulated genes in microglia.

Main Methods:

  • Analysis of microglia activation markers and phagocytic activity during postnatal development.
  • Assessment of Tgfβ signaling pathways within microglia.
  • Investigation of Tgfβ1 expression in neurons.
  • Identification of Tgfβ1 target genes in microglia using molecular techniques.

Main Results:

  • Early postnatal microglia maturation is characterized by alternative activation, increased engulfment of apoptotic cells, and activated Tgfβ signaling.
  • Microglial Tgfβ signaling precedes the induction of microglia-specific gene expression, underscoring Tgfβ1's critical role.
  • Neurons express Tgfβ1 in both postnatal and adult brains, establishing neuron-microglia communication.
  • Tmem119, a novel microglia marker, is identified as a direct target of Tgfβ1-Smad2 signaling.

Conclusions:

  • Tgfβ1 is a pivotal mediator of postnatal microglia maturation and maintenance.
  • Neuron-microglia communication via Tgfβ1 is essential for brain development and homeostasis.
  • Tgfβ1 signaling influences microglia-specific gene expression, including the marker Tmem119.

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