Fractalkine Signaling and Microglia Functions in the Developing Brain.
Microglial cells are the resident macrophages of the central nervous system (CNS). Besides their classical roles in pathological conditions, these immune cells also dynamically interact with neurons and influence their structure and function in physiological conditions. The neuronal chemokine fractalkine and its microglial receptor CX3CR1 are one important signaling pathway involved in these reciprocal interactions. In the present review, we will discuss recent evidence indicating that fractalkine signaling also determines several functions of microglial cells during normal CNS development. It has been known for a decade that microglial cells influence the neuronal death that normally occurs during CNS development. Surprisingly, recent evidence indicates that they can also support survival of developing neurons, control axon outgrowth, and laminar positioning of subsets of interneurons in the forebrain. Moreover, microglial cells influence the maturation of synaptic circuits at early postnatal stages: their phagocytic activity allows them to eliminate inappropriate synapses and they can also influence the functional expression of synaptic proteins by releasing mediators. Fractalkine signaling controls these functions of microglial cells in part by regulating their timely recruitment at sites of developing synapses. Finally, on-going research suggests that this signaling pathway is also a key player in neurodevelopmental disorders.
Institut National de la Santé et de la Recherche Médicale (INSERM), U1128, 75006 Paris, France ; Université Paris Descartes, 75006 Paris, France ; Focus Program Translational Neuroscience (FTN) and Institute for Microscopic Anatomy and Neurobiology, Johannes Gutenberg University Mainz, Hanns-Dieter-Hüsch-Weg 19, 55128 Mainz, Germany.
Isabelle
I
Arnoux
Institut National de la Santé et de la Recherche Médicale (INSERM), U1128, 75006 Paris, France ; Université Paris Descartes, 75006 Paris, France.
Etienne
E
Audinat
D000818:Animals; D001921:Brain / Q000254:growth & development* / Q000502:physiology*; D054428:Chemokine CX3CL1 / Q000502:physiology*; D006801:Humans; D017628:Microglia / Q000502:physiology*; D015398:Signal Transduction; D013569:Synapses / Q000502:physiology
D054428:Chemokine CX3CL1