The behavior and functions of embryonic microglia

Abstract

Microglia are the resident immune cells of the central nervous system. Microglial progenitors are generated in the yolk sac during the early embryonic stage. Once microglia enter the brain primordium, these cells colonize the structure through migration and proliferation during brain development. Microglia account for a minor population among the total cells that constitute the developing cortex, but they can associate with many surrounding neural lineage cells by extending their filopodia and through their broad migration capacity. Of note, microglia change their distribution in a stage-dependent manner in the developing brain: microglia are homogenously distributed in the pallium in the early and late embryonic stages, whereas these cells are transiently absent from the cortical plate (CP) from embryonic day (E) 15 to E16 and colonize the ventricular zone (VZ), subventricular zone (SVZ), and intermediate zone (IZ). Previous studies have reported that microglia positioned in the VZ/SVZ/IZ play multiple roles in neural lineage cells, such as regulating neurogenesis, cell survival and neuronal circuit formation. In addition to microglial functions in the zones in which microglia are replenished, these cells indirectly contribute to the proper maturation of post-migratory neurons by exiting the CP during the mid-embryonic stage. Overall, microglial time-dependent distributional changes are necessary to provide particular functions that are required in specific regions. This review summarizes recent advances in the understanding of microglial colonization and multifaceted functions in the developing brain, especially focusing on the embryonic stage, and discuss the molecular mechanisms underlying microglial behaviors.

Maternal SARS-CoV-2 impacts fetal placental macrophage programs and placenta-derived microglial models of neurodevelopment

“…Interestingly, HBC 3 – in which “Inflammation of Central Nervous System” is also predicted to be activated after maternal SARS-CoV-2 infection and whose transcriptional signature is consistent with activation in phagocytosis pathways, also implicates increased “Apoptosis of neurons” and “Neuronal cell death” (Figure 3B). In a developmental context, this pattern may represent a functional rather than pathologic gene signature in response to SARS-CoV-2, as microglia (resident brain macrophages) play a key role in neuronal cell turnover, regulation of neural progenitors, and synaptic rewiring in early neurodevelopment, all via phagocytosis (56). Thus, increased phagocytosis by tissue-resident macrophages might be an adaptive response to SARS-CoV-2-associated inflammation, while reduced phagocytosis could be a pathologic or maladaptive response to maternal immune activation (e.g., reduced microglial phagocytosis and reduced synaptic pruning associated with maternal immune activation is thought to be a key aspect of the pathogenesis of autism (57–59)).…”

Impact of Maternal Ketogenic Diet on NLRP3 Inflammasome Response in the Offspring Brain

“…In the offspring, the DG, CA1, and PFC areas showed increased microglial cells and enhanced NLRP3 expression following exposure to the KD, which operated rather as an insult to the developing brain. Embryonic microglia have multifaceted functions in the developing brain, and molecular mechanisms underlying embryonic microglial behaviors may be completely different from adult microglia [37]. Alternatively, NLRP3 expression was significantly lower in the KD + LPS group when compared to the SD + LPS group in the DG and CA1 regions.…”

p27kip1 Modulates the Morphology and Phagocytic Activity of Microglia

“…Microglial cells do acquire this active migration speed to reach their final position in the brain. Alterations in microglial positioning may affect brain development, i.e., neurogenesis, neuronal circuit development, or cell survival [ 67 ]. Secondly, in a pathological context, microglial cells require extensive cell body migration to promote both CNS damage and repair [ 68 ].…”