Microglia: Architects of the Developing Nervous System

Abstract

Microglia are resident macrophages of the central nervous system (CNS), representing 5-10% of total CNS cells. Recent findings reveal that microglia enter the embryonic brain, take up residence before the differentiation of other CNS cell types, and become critical regulators of CNS development. Here, we discuss exciting new work implicating microglia in a range of developmental processes, including regulation of cell number and spatial patterning of CNS cells, myelination, and formation and refinement of neural circuits. Furthermore, we review studies suggesting that these cellular functions result in the modulation of behavior, which has important implications for a variety of neurological disorders.

Keywords: central nervous system; development; microglia.

Figure 1. Microglia interact with developing cells in the postnatal brain

A, Microglia (green) in the juvenile (P30) mouse hippocampus represent 5–10% of total CNS cells. Microglia are labeled using a transgenic reporter (CX3CR1^egfp/WT) and neurons are labeled with an antibody directed against NeuN (purple). Scale bar=100µm. B, Microglia (Cx3CR1^egfp/WT, green) in the SVZ of a P13 mouse engulfing actively dividing cells labeled with 5-ethynyl-2’-deoxyuridine (EDU; purple). Often these apoptotic, dividing cells are found enveloped within microglial processes that form phagocytic cups (arrow and enlarged in inset). C, Microglia (CX3CR1^egfp/WT, green) closely associate and often contact (arrow and inset) retinal ganglion cell (RGC) presynaptic inputs labeled by anterograde tracing with cholera toxin β subunit conjugated to Alexa 594 (CTB-594, purple) in the juvenile mouse lateral geniculate nucleus (LGN, P29). Di, Microglia (CX3CR1^egfp/WT, green) in the early postnatal LGN (P5) closely associate with RGC presynaptic inputs (CTB-594, purple). Dii, Engulfment of presynaptic inputs can be visualized within the microglia soma and processes (arrow, inset) once all RGC input fluorescence outside the microglia volume is subtracted. B–D, Scale bar=10µm.

Figure 2. Key Figure. A summary of microglia functions in the developing brain

New data demonstrate that microglia can affect the development of other resident CNS cell types throughout the CNS. NPC, neural precursor cell; OPC, oligodendrocyte precursor cell.