Microglia maintain structural integrity during fetal brain morphogenesis

Spatiotemporal dynamics of the CD11c+ microglial population in the mouse brain and spinal cord from developmental to adult stages

“…Thus, microglia in the brain and spinal cord acquire the CD11c + state from the prenatal stage, but their regulation and role in CNS development are distinct between the pre- and postnatal phases. Consistently, a recent study conducting the comprehensive transcriptomic analysis of microglia during the early embryonic stage and their role in prenatal development demonstrated that microglia at E15 have a core gene signature characterized in previously reported postnatal ATM, including Itgax , Spp1 and Clec7a , genes that are shared with CD11c + microglia, and that prenatal ATM-like microglia have repair properties that are necessary for the maintenance of structural integrity during the development of the cerebral cortex [ 15 ].…”

“…In summary, our longitudinal comparative study of CD11c + microglia from the early postnatal to adult CNS demonstrated that the spatial and temporal dynamics of this population vary between the brain and spinal cord regions. In humans, CD11c + microglia-resembling population has recently been found in the brain during the developmental and adult stages, and disease conditions [ 4 , 15 , 33 ]. Our findings improve our understanding of the nature of microglial heterogeneity and its dynamics in the CNS.…”

“…One of the highly upregulated genes in DAM and similar microglial states is Itgax [ 3 , 9 – 11 ], which encodes integrin αX (also known as CD11c). CD11c + microglia [ 8 , 11 – 15 ] and various other microglial populations (for example, axon tract-associated microglia (ATM) [ 7 ], proliferative region-associated microglia (PAM) [ 6 ], youth-associated microglia (YAM) [ 16 ], and Arginase-1 + microglia [ 17 ]) have also been found in the pre/postnatal developing and adult brains of mice and humans. The core signature gene shared by these populations is Itgax [ 6 , 7 , 11 , 16 , 17 ].…”

“…The core signature gene shared by these populations is Itgax [ 6 , 7 , 11 , 16 , 17 ]. The role of each distinct microglial population in health and disease remains to be fully understood; however, CD11c + microglia and similar populations have recently been implicated in pre/postnatal brain development [ 15 , 17 ], myelination [ 12 , 18 ], and CNS diseases [ 11 ] such as AD [ 3 , 9 , 14 , 19 ], multiple sclerosis [ 9 , 12 , 18 , 20 ], and chronic pain [ 21 , 22 ].…”

“…It has previously been shown that the abundance of the CD11c + population increases during early postnatal development and with aging [ 12 , 13 , 23 ]; however, the spatiotemporal dynamics of CD11c + microglia in individual CNS regions remain to be determined. This seems to be important because recent studies have shown that the distribution of microglia is not uniform in each brain region during development, and that the uneven spatial pattern is implicated in site-specific structural maintenance and neuronal generation/migration/wiring [ 8 , 15 , 24 ].…”