Multifaceted microglia during brain development: Models and tools

Abstract

Microglia, the brain resident macrophages, are multifaceted glial cells that belong to the central nervous and immune systems. As part of the immune system, they mediate innate immune responses, regulate brain homeostasis and protect the brain in response to inflammation or injury. At the same time, they can perform a wide array of cellular functions that relate to the normal functioning of the brain. Importantly, microglia are key actors of brain development. Indeed, these early brain invaders originate outside of the central nervous system from yolk sac myeloid progenitors, and migrate into the neural folds during early embryogenesis. Before the generation of oligodendrocytes and astrocytes, microglia thus occupy a unique position, constituting the main glial population during early development and participating in a wide array of embryonic and postnatal processes. During this developmental time window, microglia display remarkable features, being highly heterogeneous in time, space, morphology and transcriptional states. Although tremendous progress has been made in our understanding of their ontogeny and roles, there are several limitations for the investigation of specific microglial functions as well as their heterogeneity during development. This review summarizes the current murine tools and models used in the field to study the development of these peculiar cells. In particular, we focus on the methodologies used to label and deplete microglia, monitor their behavior through live-imaging and also discuss the progress currently being made by the community to unravel microglial functions in brain development and disorders.

The niche matters: origin, function and fate of CNS-associated macrophages during health and disease

“…In rodents, clusters of vascular endothelial-like cells are present in the developing CNS at E7.5–E8.5 [ 115 ] and start to organize into a branched vascular network by E9.5 [ 109 ], which correlates with microglia seeding of the CNS. Microglia exploit the forming vascular structures as paths to infiltrate into the CNS [ 6 ] and colonize the CNS in a heterogeneous spatiotemporal pattern, with transient accumulation in selected hotspots, i.e., the cortico-striatal-amygdalar boundary, before distributing throughout the brain and developing site-specific morphological and phenotypical features [ 10 ]. As discussed above, mature microglia have a typical gene profile, with Hexb, P2ry12 , Tmem119 , Sall1 and Siglech representing homeostatic markers [ 62 ].…”

CB2 expression in mouse brain: from mapping to regulation in microglia under inflammatory conditions

“…This may suggest that CB2 is predominantly expressed by cells with a supporting role in the CNS, rather than cells with a highly specialized role. Although subtle differences in terms of density and phenotype are beginning to be identi ed in certain brain regions, microglial cells are present throughout the nervous system and play a crucial homeostatic role [33][34][35]. Furthermore, CB2 is known to be mostly expressed at the periphery by leukocytes, including myeloid monocytes and macrophages [1,36,37], leading to the hypothesis that microglia may be one of the main cells expressing CB2 in the CNS.…”