Table 1.

Examples of developmental functions of microglia

Function	Promotes / Facilitates	Inhibits / Eliminates
Progenitor proliferation	•MCM increases cerebellar progenitor proliferation (Morgan et al., 2004). •PU.1−/− mice lack microglia.Neural precursor cell proliferation is reduced and rescued by adding microglia (Antony et al., 2011). •Csf1r knockouts have few microglia with cortical thinning, effects on proliferation and neuron production (Erblich et al., 2011; Nandi et al., 2012). But note direct effects of Csf1r in progenitors (Chitu et al., 2016).	•Microglia have no effect on proliferation in cultures of postnatal subventricular neurospheres (Walton et al., 2006).
Neuronal and glial differentiation	•Microglia promote neuronal differentiation of neural precursor cells (Aarum et al., 2003). •IL-4 treated microglia promote oligodendrogenesis while IFN-γ activated microglia enhance neurogenesis (Butovsky et al., 2006b). •Inhibiting microglia decreases neurogenesis and oligodendrogenesis in postnatal cortex (Shigemoto-Mogami et al., 2014). •IL-1β, IL-6, TNF-α, and IFN-γ enhance neurogenesis and oligodendrogenesis in vitro (Shigemoto-Mogami et al., 2014). •Microglia or MCM promote neurogenesis of postnatal subventricular neurospheres (Walton et al., 2006). •PU.1−/− cultures have reduced astrogenesis (Antony et al., 2011). •Microglial IL-6 and LIF promote the differentiation of astrocytes (Nakanishi et al., 2007).	•Microglial Il-6 suppresses neurosphere generation from adult retinal cell suspensions (Balasubramaniam et al., 2009).
Adult neurogenesis	•Microglia in SVZ required for survival and migration of neuroblasts through the rostral migratory stream (Ribeiro Xavier et al., 2015) and in culture (Aarum et al., 2003). •Fractalkine signaling mediates exercise-induced increases in neurogenesis (Vukovic et al., 2012). •Exercise increased the proportion of microglia expressing Igf1 (Kohman et al., 2012).	•Microglia engulf newly generated neuroblasts in the adult SGZ (Sierra et al., 2010). •Microglia in proliferative zones undergo age-related changes associated with reductions in neural stem cell proliferation and differentiation (Solano Fonseca et al., 2016). •Depleting microglia in aged animals increases neurogenesis (Vukovic et al., 2012). • Exogenous fractalkine reverses age-related deficits in neurogenesis (Bachstetter et al., 2011).
Neuronal and progenitor survival	•Microglia or conditioned medium increase survival of rat cerebellar granule neurons in culture (Morgan et al., 2004). •Microglia are required for the survival of developing layer V cortical neurons, in part by secretion of Igf1 (Ueno et al., 2013).	•Microglia stimulate neuronal apoptosis through production of reactive oxygen species in cerebellum (Marín-Teva et al., 2004). •Microglial-mediated neuronal apoptosis requires Cd11b and Dap12 in developing hippocampus (Wakselman et al., 2008). •Microglial NGF stimulates RGC death via p75 (Frade and Barde, 1998). •Microglia engulf cortical neural precursor cells to limit neuron generation in embryo (Cunningham et al., 2013).
Neural circuit development	•Microglia required for laminar positioning of subsets of interneurons in somatosensory cortex (Squarzoni et al., 2014). •Microglia facilitate axon fasciculation in corpus callosum (Pont-Lezica et al., 2014a). •Microglia promote axon myelination (Hagemeyer et al., 2017; Wlodarczyk et al., 2017). •Microglial-derived BDNF is required for learning-dependent spine remodeling and formation. Disruption results in deficits in multiple learning tasks (Parkhurst et al., 2013). •Synapse formation in the somatosensory cortex (Miyamoto et al., 2016).	•Microglia limit outgrowth of dopaminergic axons in the forebrain (Squarzoni et al., 2014). •Microglia eliminate excessive synapses from RGCs in the lateral geniculate nucleus (Stevens et al., 2007; Schafer et al., 2012). •In postnatal mouse hippocampus, microglial synaptic engulfment is required for normal synaptic maturation, functional connectivity, and behavior (Paolicelli et al., 2011; Zhan et al., 2014).