Greater Number of Microglia in Telencephalic Proliferative Zones of Human and Nonhuman Primate Compared with Other Vertebrate Species

Abstract

Microglial cells, the innate immune cells of the brain, are derived from yolk sac precursor cells, begin to colonize the telencephalon at the onset of cortical neurogenesis, and occupy specific layers including the telencephalic proliferative zones. Microglia are an intrinsic component of cortical germinal zones, establish extensive contacts with neural precursor cells (NPCs) and developing cortical vessels, and regulate the size of the NPC pool through mechanisms that include phagocytosis. Microglia exhibit notable differences in number and distribution in the prenatal neocortex between rat and Old World nonhuman primate telencephalon, suggesting that microglia exhibit distinct properties across vertebrate species. To begin addressing this subject we quantified the number of microglia and NPCs in proliferative zones of the fetal human, rhesus monkey, ferret, and rat, and the pre-hatch chick and turtle telencephalon. We show that the ratio of NPCs to microglia varies significantly across species. Few microglia populate the pre-hatch chick telencephalon, but the number of microglia approaches that of NPCs in fetal human and non-human primate telencephalon. These data demonstrate that microglia are in a position to perform similar functions in a number of vertebrate species, but more heavily colonize proliferative zones of fetal human and rhesus monkey telencephalon.

Microglial contribution to the pathology of neurodevelopmental disorders in humans

“…1 ). Although studies involving human microglia can be complex, research on chimeric models that involve transplanting human-induced pluripotent stem cells (hiPSCs)-derived microglial progenitor cells [ 41 , 66 ] or microglia [ 107 ] into the mouse brain, human brain organoids [ 41 ], and embryonic and fetal tissues [ 149 ] have confirmed previous findings in animal models. In humans, microglia have been linked with crucial developmental processes such as neurogenesis, programmed cell death and apoptotic cell clearance, neuronal migration, white matter tract formation, and synaptic pruning [ 119 ].…”

“…These varying morphologies likely correspond to specific functions notably associated with the neuroanatomical process or compartment they inhabit or attempt to colonise, the stage of life (development, adulthood, or ageing), the sex of the individual, and the challenges they encounter (disease, injury, etc.) across life, as revealed by morphological, ultrastructural, epigenetic, transcriptomic, metabolomic, and proteomic data [ 9 , 111 , 120 , 121 , 149 , 161 ]. For instance, intermediate rod-shaped microglia are observed in white matter tracts, such as the corpus callosum and the external capsule, towards the end of the 30th pcw where they suggestively participate in axonal guidance, synaptogenesis, and neurodevelopmental apoptosis [ 204 ].…”

Role of microglia in brain development after viral infection

“…Microglia colonize the developing brain early before neuro/gliogenesis, neuronal wiring, and many other cellular processes, suggesting their non-innate immune roles in supporting the brain development ( Tay et al, 2017 ; Thion and Garel, 2017 ; Menassa and Gomez-Nicola, 2018 ; Mehl et al, 2022 ). They entry the brain rudiment in a stepwise manner and occupy specific layers of the prenatal cerebral cortex including the telencephalic proliferative zones, where they establish extensive contacts with neural precursor cells (NPCs) and developing cortical vessels ( Monier et al, 2007 ; Matcovitch-Natan et al, 2016 ; Menassa and Gomez-Nicola, 2018 ; Tan et al, 2020 ; Penna et al, 2021a ; Penna et al, 2021b ). They help shape the newly formed CNS through regulating neurogenesis in multiple proliferative brain regions by phagocytic and secretory mechanisms ( Lenz and Nelson, 2018 ; Mehl et al, 2022 ).…”