Abstract
Physiological functions require coordination of processes between diverse organs, tissues, and cells. This integrative view of science has reemerged complementary to the reductionist philosophy of studying individual cell types. An integrative approach has proven particularly powerful within the field of neuroscience where, intermingled among the most numerous neural cell types of the brain, are immune cells called microglia. Microglia act as a line of defense in the CNS by phagocytizing harmful pathogens and cellular debris and by releasing a variety of factors that mediate immune responses. However, microglia are also appreciated as critical mediators of neurophysiology making them a desired target to rectify neuropathological states. The goal of this review is to discuss microglia ontogenesis, referred to as microgliogenesis, a term that encompasses the events that drive the production, differentiation, migration, and maturation of microglia and opportunities to target microglia for brain repair.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aaku-Saraste E, Hellwig A, Huttner WB (1996) Loss of occludin and functional tight junctions, but not ZO-1, during neural tube closure—remodeling of the neuroepithelium prior to neurogenesis. Dev Biol 180:664–679. https://doi.org/10.1006/dbio.1996.0336
Abels ER, Broekman MLD, Breakefield XO, Maas SLN (2019) Glioma EVs contribute to immune privilege in the brain. Trends in Cancer 5:393–396. https://doi.org/10.1016/j.trecan.2019.05.006
Ajami B, Bennett JL, Krieger C et al (2007) Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nat Neurosci 10:1538–1543. https://doi.org/10.1038/nn2014
Altman J (1962) Autoradiographic study of degenerative and regenerative proliferation of neuroglia cells with tritiated thymidine. Exp Neurol 5:302–318
Alvarez-Buylla A, García-Verdugo JM, Tramontin AD (2001) A unified hypothesis on the lineage of neural stem cells. Nat Rev Neurosci 2:287–293. https://doi.org/10.1038/35067582
Arnò B, Grassivaro F, Rossi C et al (2014) Neural progenitor cells orchestrate microglia migration and positioning into the developing cortex. Nat Commun 5:1–13. https://doi.org/10.1038/ncomms6611
Askew K, Li K, Olmos-Alonso A et al (2017) Coupled proliferation and apoptosis maintain the rapid turnover of microglia in the adult brain. Cell Rep 18:391–405. https://doi.org/10.1016/j.celrep.2016.12.041
Bennett FC, Bennett ML, Yaqoob F et al (2018) A combination of ontogeny and CNS environment establishes microglial identity. Neuron 98:1170–1183. https://doi.org/10.1016/j.neuron.2018.05.014
Bennett ML, Bennett FC, Liddelow SA et al (2016) New tools for studying microglia in the mouse and human CNS. Proc Natl Acad Sci U S A 113:E1738–E1746. https://doi.org/10.1073/pnas.1525528113
Blennow K, Brody DL, Kochanek PM et al (2016) Traumatic brain injuries. Nat Rev Dis Prim 2. https://doi.org/10.1038/nrdp.2016.84
Bohlen CJ, Bennett FC, Tucker AF et al (2017) Diverse requirements for microglial survival, specification, and function revealed by defined-medium cultures. Neuron 94:759–773. https://doi.org/10.1016/j.neuron.2017.04.043
Boya J, Calvo J, Prado A (1979) The origin of microglial cells. J Anat 129:177–186. https://doi.org/10.1038/nrn2960
Butovsky O, Jedrychowski MP, Moore CS et al (2014) Identification of a unique TGF-β-dependent molecular and functional signature in microglia. Nat Neurosci 17:131–147. https://doi.org/10.1038/nn.3599
Catalano M, O’Driscoll L (2020) Inhibiting extracellular vesicles formation and release: a review of EV inhibitors. J Extracell Vesicles 9. https://doi.org/10.1080/20013078.2019.1703244
Chau KF, Springel MW, Broadbelt KG et al (2015) Progressive differentiation and instructive capacities of amniotic fluid and cerebrospinal fluid proteomes following neural tube closure. Dev Cell 35:789–802. https://doi.org/10.1016/j.devcel.2015.11.015
Chen HR, Sun YY, Chen CW et al (2020) Fate mapping via CCR2-CreER mice reveals monocyte-to-microglia transition in development and neonatal stroke. Sci Adv 6:1–13. https://doi.org/10.1126/sciadv.abb2119
Corps KN, Roth TL, McGavern DB (2015) Inflammation and neuroprotection in traumatic brain injury. JAMA Neurol 72:355–362. https://doi.org/10.1001/jamaneurol.2014.3558
Cossetti C, Iraci N, Mercer TR et al (2014) Extracellular vesicles from neural stem cells transfer IFN-γ via Ifngr1 to activate Stat1 signaling in target cells. Mol Cell 56:193–204. https://doi.org/10.1016/j.molcel.2014.08.020
Coulter ME, Dorobantu CM, Lodewijk GA et al (2018) The ESCRT-III protein CHMP1A mediates secretion of sonic hedgehog on a distinctive subtype of extracellular vesicles. Cell Rep 24:973–986. https://doi.org/10.1016/j.celrep.2018.06.100
Cunningham CL, Martínez-Cerdeño V, Noctor SC (2013) Microglia regulate the number of neural precursor cells in the developing cerebral cortex. J Neurosci 33:4216–4233. https://doi.org/10.1523/JNEUROSCI.3441-12.2013
De Carlos JA, López-Mascaraque L, Valverde F (1996) Dynamics of cell migration from the lateral ganglionic eminence in the rat. J Neurosci 16:6146–6156. https://doi.org/10.1523/jneurosci.16-19-06146.1996
Deshmane SL, Kremlev S, Amini S, Sawaya BE (2009) Monocyte chemoattractant protein-1 (MCP-1): an overview. J Interf Cytokine Res 29:313–326. https://doi.org/10.1089/jir.2008.0027
Elkabes S, DiCicco-Bloom EM, Black IB (1996) Brain microglia/macrophages express neurotrophins that selectively regulate microglial proliferation and function. J Neurosci 16:2508–2521. https://doi.org/10.1523/jneurosci.16-08-02508.1996
Erblich B, Zhu L, Etgen AM et al (2011) Absence of colony stimulation factor-1 receptor results in loss of microglia, disrupted brain development and olfactory deficits. PLoS One 6:1–13. https://doi.org/10.1371/journal.pone.0026317
Estes ML, McAllister AK (2016) Maternal immune activation: implications for neuropsychiatric disorders. Science (80) 353:772–777. https://doi.org/10.1126/science.aag3194
Falcão AM, Marques F, Novais A et al (2012) The path from the choroid plexus to the subventricular zone: go with the flow! Front Cell Neurosci 6:1–8. https://doi.org/10.3389/fncel.2012.00034
Fame RM, Lehtinen MK (2020) Emergence and developmental roles of the cerebrospinal fluid system. Dev Cell 52:261–275. https://doi.org/10.1016/j.devcel.2020.01.027
Feliciano DM, Zhang S, Nasrallah CM et al (2014) Embryonic cerebrospinal fluid nanovesicles carry evolutionarily conserved molecules and promote neural stem cell amplification. PLoS One 9:1–10. https://doi.org/10.1371/journal.pone.0088810
Flanders KC, Ren RF, Lippa CF (1998) Transforming growth factor-βS in neurodegenerative disease. Prog Neurobiol 54:71–85. https://doi.org/10.1016/S0301-0082(97)00066-X
Forstreuter F, Lucius R, Mentlein R (2002) Vascular endothelial growth factor induces chemotaxis and proliferation of microglial cells. J Neuroimmunol 132:93–98. https://doi.org/10.1016/S0165-5728(02)00315-6
Füger P, Hefendehl JK, Veeraraghavalu K et al (2017) Microglia turnover with aging and in an Alzheimer’s model via long-term in vivo single-cell imaging. Nat Neurosci 20:1371–1378. https://doi.org/10.1038/nn.4631
Furth R, Cohn Z (1968) The origin and kinetics of mononuclear phagocytes. J Exp Med 128:415–435
Ge WP, Miyawaki A, Gage FH et al (2012) Local generation of glia is a major astrocyte source in postnatal cortex. Nature 484:376–381. https://doi.org/10.1038/nature10959
Ginhoux F, Greter M, Leboeuf M et al (2010) Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science (80) 330:841–845. https://doi.org/10.1126/science.1194637
Goldmann T, Wieghofer P, Jordão MJC et al (2016) Origin, fate and dynamics of macrophages at central nervous system interfaces. Nat Immunol 17:797–807. https://doi.org/10.1038/ni.3423
Greter M, Lelios I, Pelczar P et al (2012) Stroma-derived interleukin-34 controls the development and maintenance of Langerhans cells and the maintenance of microglia. Immunity 37:1050–1060. https://doi.org/10.1016/j.immuni.2012.11.001
Groblewska M, Litman-Zawadzka A, Mroczko B (2020) The role of selected chemokines and their receptors in the development of gliomas. Int J Mol Sci 21:1–52. https://doi.org/10.3390/ijms21103704
Guedes V, Devoto C, Leete J et al (2020) Extracellular vesicle proteins and microRNAs as biomarkers for traumatic brain injury. Front Neurol 11:1–18. https://doi.org/10.3389/fneur.2020.00663
Hagemeyer N, Hanft KM, Akriditou MA et al (2017) Microglia contribute to normal myelinogenesis and to oligodendrocyte progenitor maintenance during adulthood. Acta Neuropathol 134:441–458. https://doi.org/10.1007/s00401-017-1747-1
Hambardzumyan D, Gutmann DH, Kettenmann H (2016) The role of microglia and macrophagesin glioma maintenance and progression. Nat Neurosci 19:20–27. https://doi.org/10.1002/jmri.25711.PET/MRI
Hammond TR, Dufort C, Dissing-Olesen L et al (2019) Single-cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes. Immunity 50:253-271.e6. https://doi.org/10.1016/j.immuni.2018.11.004
Hansen DV, Lui JH, Parker PRL, Kriegstein AR (2010) Neurogenic radial glia in the outer subventricular zone of human neocortex. Nature 464:554–563. https://doi.org/10.1038/nature08845
Hartfuss E, Galli R, Heins N, Götz M (2001) Characterization of CNS precursor subtypes and radial glia. Dev Biol 229:15–30. https://doi.org/10.1006/dbio.2000.9962
Hazelton I, Yates A, Dale A et al (2018) Exacerbation of acute traumatic brain injury by circulating extracellular vesicles. J Neurotrauma 35:639–651. https://doi.org/10.1089/neu.2017.5049
Henry RJ, Ritzel RM, Barrett JP et al (2020) Microglial depletion with CSF1R inhibitor during chronic phase of experimental traumatic brain injury reduces neurodegeneration and neurological deficits. J Neurosci 40:2960–2974. https://doi.org/10.1101/791871
Hirasawa T, Ohsawa K, Imai Y et al (2005) Visualization of microglia in living tissues using Iba1-EGFP transgenic mice. J Neurosci Res 81:357–362. https://doi.org/10.1002/jnr.20480
Huang Y, Xu Z, Xiong S et al (2018) Repopulated microglia are solely derived from the proliferation of residual microglia after acute depletion. Nat Neurosci 21:530–540. https://doi.org/10.1038/s41593-018-0090-8
Hyder AA, Wunderlich CA, Puvanachandra P et al (2007) The impact of traumatic brain injuries: a global perspective. NeuroRehabilitation 22:341–353. https://doi.org/10.3233/nre-2007-22502
Iraci N, Gaude E, Leonardi T et al (2017) Extracellular vesicles are independent metabolic units with asparaginase activity. Nat Chem Biol 13:951–955. https://doi.org/10.1038/nchembio.2422
Jassam YN, Izzy S, Whalen M et al (2017) Neuroimmunology of traumatic brain injury: time for a paradigm shift. Neuron 95:1246–1265. https://doi.org/10.1016/j.neuron.2017.07.010
Johanson CE, Stopa EG, McMillan PN (2011) The blood-cerebrospinal fluid barrier: structure and functional significance. Methods Mol Biol 686:101–131
Kenney K, Qu BX, Lai C et al (2018) Higher exosomal phosphorylated tau and total tau among veterans with combat-related repetitive chronic mild traumatic brain injury. Brain Inj 32:1276–1284. https://doi.org/10.1080/02699052.2018.1483530
Kierdorf K, Erny D, Goldmann T et al (2013) Microglia emerge from erythromyeloid precursors via Pu.1-and Irf8-dependent pathways. Nat Neurosci 16:273–282. https://doi.org/10.1038/nn.3318
Kriegstein AR, Götz M (2003) Radial glia diversity: a matter of cell fate. Glia 43:37–43. https://doi.org/10.1002/glia.10250
Laulagnier K, Motta C, Hamdi S et al (2004) Mast cell- and dendritic cell-derived exosomes display a specific lipid composition and an unusual membrane organization. Biochem J 380:161–171. https://doi.org/10.1042/BJ20031594
Lavdas AA, Grigoriou M, Pachnis V, Parnavelas JG (1999) The medial ganglionic eminence gives rise to a population of early neurons in the developing cerebral cortex. J Neurosci 99:7881–7888. https://doi.org/10.1523/jneurosci.19-18-07881.1999
Lee DA, Bedont JL, Pak T et al (2012) Tanycytes of the hypothalamic median eminence form a diet-responsive neurogenic niche. Nat Neurosci 15:700–704. https://doi.org/10.1038/nn.3079
Lehtinen MK, Zappaterra MW, Chen X et al (2011) The cerebrospinal fluid provides a proliferative niche for neural progenitor cells. Neuron 69:893–905. https://doi.org/10.1016/j.neuron.2011.01.023
Levin HS, Diaz-Arrastia RR (2015) Diagnosis, prognosis, and clinical management of mild traumatic brain injury. Lancet Neurol 14:506–517. https://doi.org/10.1016/S1474-4422(15)00002-2
Lewis PD (1968) The fate of the subependymal cell in the adult rat brain, with a note on the origin of microglia. Brain A J Neurol 91:721–736
Li Q, Barres BA (2018) Microglia and macrophages in brain homeostasis and disease. Nat Rev Immunol 18:225–242. https://doi.org/10.1038/nri.2017.125
Li Q, Cheng Z, Zhou L et al (2019) Developmental heterogeneity of microglia and brain myeloid cells revealed by deep single-cell RNA sequencing. Neuron 101:207–223. https://doi.org/10.1016/j.neuron.2018.12.006
Lim DA, Alvarez-Buylla A (2016) The adult ventricular–subventricular zone (V-SVZ) and olfactory bulb (OB) neurogenesis. Cold Spring Harb Perspect Biol 8:1–33. https://doi.org/10.1101/cshperspect.a018820
Lin H, Lee E, Hestir K et al (2008) Discovery of a cytokine and its receptor by functional screening of the extracellular proteome. Science (80) 320:807–811
Ling EA (1976) Some aspects of amoeboid microglia in the corpus callosum and neighbouring regions of neonatal rats. J Anat 121:29–45
Ling EA, Wong WC (1984) A scanning and transmission electron microscopic study of amoeboid microglia cells in the prenatal rat brain following a maternal injection of 6-aminonicotinamide. J Anat 138:733–743
Liu B, Hong JS (2003) Role of microglia in inflammation-mediated neurodegenerative diseases: mechanisms and strategies for therapeutic intervention. J Pharmacol Exp Ther 304:1–7. https://doi.org/10.1124/jpet.102.035048
Long X, Yao X, Jiang Q et al (2020) Astrocyte-derived exosomes enriched with miR-873a-5p inhibit neuroinflammation via microglia phenotype modulation after traumatic brain injury. J Neuroinflammation 17:1–15. https://doi.org/10.1186/s12974-020-01761-0
Lun MP, Johnson MB, Broadbelt KG et al (2015) Spatially heterogeneous choroid plexus transcriptomes encode positional identity and contribute to regional CSF production. J Neurosci 35:4903–4916. https://doi.org/10.1523/JNEUROSCI.3081-14.2015
Luo J, Elwood F, Britschgi M et al (2013) Colony-stimulating factor 1 receptor (CSF1R) signaling in injured neurons facilitates protection and survival. J Exp Med 210:157–172. https://doi.org/10.1084/jem.20120412
Luskin MBMB (1993) Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone. Neuron 11:173–189. https://doi.org/10.1016/0896-6273(93)90281-U
Maas SLN, Abels ER, Van De Haar LL et al (2020) Glioblastoma hijacks microglial gene expression to support tumor growth. J Neuroinflammation 17:1–18. https://doi.org/10.1186/s12974-020-01797-2
Malatesta P, Hack MA, Hartfuss E et al (2003) Neuronal or glial progeny: regional differences in radial glia fate. Neuron 37:751–764. https://doi.org/10.1016/S0896-6273(03)00116-8
Markovic DS, Vinnakota K, Chirasani S et al (2009) Gliomas induce and exploit microglial MT1-MMP expression for tumor expansion. Proc Natl Acad Sci U S A 106:12530–12535. https://doi.org/10.1073/pnas.0804273106
Masuda T, Sankowski R, Staszewski O et al (2019) Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution. Nature 566:388–392. https://doi.org/10.1038/s41586-019-0924-x
Matcovitch-Natan O, Winter DR, Giladi A et al (2016) Microglia development follows a stepwise program to regulate brain homeostasis. Science (80) 353:1–19. https://doi.org/10.1126/science.aad8670
Merkle FT, Tramontin AD, García-Verdugo JM, Alvarez-Buylla A (2004) Radial glia give rise to adult neural stem cells in the subventricular zone. Proc Natl Acad Sci U S A 101:17528–17532. https://doi.org/10.1073/pnas.0407893101
Mildner A, Schmidt H, Nitsche M et al (2007) Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions. Nat Neurosci 10:1544–1553. https://doi.org/10.1038/nn2015
Mills CD, Kincaid K, Alt JM et al (2000) M-1/M-2 macrophages and the Th1/Th2 paradigm. J Immunol 164:6166–6173. https://doi.org/10.4049/jimmunol.164.12.6166
Mirzadeh Z, Merkle FT, Soriano-Navarro M et al (2008) Neural stem cells confer unique pinwheel architecture to the ventricular surface in neurogenic regions of the adult brain. Cell Stem Cell 3:265–278. https://doi.org/10.1016/j.stem.2008.07.004
Miyata T (2008) Development of three-dimensional architecture of the neuroepithelium: role of pseudostratification and cellular “community.” Dev Growth Differ 50:105–112. https://doi.org/10.1111/j.1440-169X.2007.00980.x
Mizrak D, Levitin HM, Delgado AC et al (2019) Single-cell analysis of regional differences in adult V-SVZ neural stem cell lineages. Cell Rep 26:394-406.e5. https://doi.org/10.1016/j.celrep.2018.12.044
Mizuno T, Doi Y, Mizoguchi H et al (2011) Interleukin-34 selectively enhances the neuroprotective effects of microglia to attenuate oligomeric amyloid-β neurotoxicity. Am J Pathol 179:2016–2027. https://doi.org/10.1016/j.ajpath.2011.06.011
Mohri I, Eguchi N, Suzuki K et al (2003) Hematopoietic prostaglandin D synthase is expressed in microglia in the developing postnatal mouse brain. Glia 42:263–274. https://doi.org/10.1002/glia.10183
Morton MC, Feliciano DM (2016) Neurovesicles in brain development. Cell Mol Neurobiol 36:409–416. https://doi.org/10.1007/s10571-015-0297-0
Morton MC, Neckles VN, Seluzicki CM et al (2018) Neonatal subventricular zone neural stem cells release extracellular vesicles that act as a microglial morphogen. Cell Rep 23:78–89. https://doi.org/10.1016/j.celrep.2018.03.037
Mosher KI, Andres RH, Fukuhara T et al (2012) Neural progenitor cells regulate microglia functions and activity. Nat Neurosci 15:1485–1489. https://doi.org/10.1038/nn.3233
Nandi S, Gokhan S, Dai XM et al (2012) The CSF-1 receptor ligands IL-34 and CSF-1 exhibit distinct developmental brain expression patterns and regulate neural progenitor cell maintenance and maturation. Dev Biol 367:100–113. https://doi.org/10.1016/j.ydbio.2012.03.026
Neckles VN, Morton MC, Holmberg JC et al (2019) A transgenic inducible GFP extracellular-vesicle reporter (TIGER) mouse illuminates neonatal cortical astrocytes as a source of immunomodulatory extracellular vesicles. Sci Rep 9:1–11. https://doi.org/10.1038/s41598-019-39679-0
Nedergaard M, Goldman SA, Lacerda de Menezes JR et al (2015) A distinct population of microglia supports adult neurogenesis in the subventricular zone. J Neurosci 35:11848–11861. https://doi.org/10.1523/jneurosci.1217-15.2015
Nimmerjahn A, Kirchhoff F, Helmchen F (2005) Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science (80) 308:1314–1318. https://doi.org/10.1515/nf-2005-0304
Noctor SC, Flint AC, Weissman TA, Dammerman RSKA (2001) Neurons derived from radial glial cells establish radial units in neocortex. Nature 409:714–720
Noctor SC, Martinez-Cerdeño V, Ivic L, Kriegstein AR (2004) Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases. Nat Neurosci 7:136–144. https://doi.org/10.1038/nn1172
Nowakowski TJ, Bhaduri A, Pollen AA et al (2017) Spatiotemporal gene expression trajectories reveal developmental hierarchies of the human cortex. Science (80) 358:1318–1323. https://doi.org/10.1126/science.aap8809
Okie S (2016) TBI’s long-term follow-up-slow progress in science and recovery. N Engl J Med 375:180–184. https://doi.org/10.1056/NEJMms1604272
Olah M, Menon V, Habib N et al (2020) Single cell RNA sequencing of human microglia uncovers a subset associated with Alzheimer’s disease. Nat Commun 11:1–18. https://doi.org/10.1038/s41467-020-19737-2
Oosterhof N, Kuil LE, van der Linde HC et al (2018) Colony-stimulating factor 1 receptor (CSF1R) regulates microglia density and distribution, but not microglia differentiation in vivo. Cell Rep 24:1203–1217. https://doi.org/10.1016/j.celrep.2018.06.113
Ormel PR, Vieira de Sá R, van Bodegraven EJ et al (2018) Microglia innately develop within cerebral organoids. Nat Commun 9:1–14. https://doi.org/10.1038/s41467-018-06684-2
Ortiz-Álvarez G, Daclin M, Shihavuddin A et al (2019) Adult neural stem cells and multiciliated ependymal cells share a common lineage regulated by the geminin family members. Neuron 102:159–172. https://doi.org/10.1016/j.neuron.2019.01.051
Paolicelli RC, Bergamini G, Rajendran L (2019) Cell-to-cell communication by extracellular vesicles: focus on microglia. Neuroscience 405:148–157. https://doi.org/10.1016/j.neuroscience.2018.04.003
Paolicelli RC, Bolasco G, Pagani F et al (2011) Synaptic pruning by microglia is necessary for normal brain development. Science (80) 333:1456–1458. https://doi.org/10.1126/science.1202529
Plate KH, Breier G, Weich HA, Risau W (1992) Vascular endothelial growth factor is a potential tumour angiogenesis factor in human glioma in vivo. Nature 359:845–848
Rakic P (2003) Elusive radial glial cells: historical and evolutionary perspective. Glia 43:19–23. https://doi.org/10.1002/glia.10244
Ramlackhansingh AF, Brooks DJ, Greenwood RJ et al (2011) Inflammation after trauma: microglial activation and traumatic brain injury. Ann Neurol 70:374–383. https://doi.org/10.1002/ana.22455
Ransohoff RM (2016) A polarizing question: do M1 and M2 microglia exist. Nat Neurosci 19:987–991. https://doi.org/10.1038/nn.4338
Raposo G, Stoorvogel W (2013) Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol 200:373–383. https://doi.org/10.1083/jcb.201211138
Rash BG, Duque A, Morozov YM et al (2019) Gliogenesis in the outer subventricular zone promotes enlargement and gyrification of the primate cerebrum. Proc Natl Acad Sci U S A 116:7089–7094. https://doi.org/10.1073/pnas.1822169116
Renee M, Elmore P, Najafi AR et al (2014) CSF1 receptor signaling is necessary for microglia viability, which unmasks a cell that rapidly repopulates the microglia-depleted adult brain. Neuron 82:380–397. https://doi.org/10.1016/j.neuron.2014.02.040.CSF1
Réu P, Khosravi A, Bernard S et al (2017) The lifespan and turnover of microglia in the human brain. Cell Rep 20:779–784. https://doi.org/10.1016/j.celrep.2017.07.004
Rojo R, Raper A, Ozdemir DD et al (2019) Deletion of a Csf1r enhancer selectively impacts CSF1R expression and development of tissue macrophage populations. Nat Commun 10:1–17. https://doi.org/10.1038/s41467-019-11053-8
Roth TL, Nayak D, Atanasijevic T et al (2013) Transcranial amelioration of inflammation and cell death after brain injury. Nature 505:223–228. https://doi.org/10.1038/nature12808
Sanai N, Nguyen T, Ihrie RA et al (2012) Corridors of migrating neurons in the human brain and their decline during infancy. Nature 478:382–386. https://doi.org/10.1038/nature10487
Schaper A (1897) The earliest differentiation in the central nervous system of Vertebrates. Science (80) 5:430–431
Schulz C, Perdiguero EG, Chorro L et al (2012) A lineage of myeloid cells independent of myb and hematopoietic stem cells. Science (80) 335:86–90. https://doi.org/10.1126/science.1219179
Shigemoto-Mogami Y, Hoshikawa K, Goldman JE et al (2014) Microglia enhance neurogenesis and oligodendrogenesis in the early postnatal subventricular zone. J Neurosci 34:2231–2243. https://doi.org/10.1523/JNEUROSCI.1619-13.2014
Sierra A, de Castro F, del Río-Hortega J et al (2016) The “Big-Bang” for modern glial biology: translation and comments on Pío del Río-Hortega 1919 series of papers on microglia. Glia 64:1801–1840. https://doi.org/10.1002/glia.23046
Sierra A, Encinas JM, Deudero JJP et al (2010) Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. Cell Stem Cell 7:483–495. https://doi.org/10.1016/j.stem.2010.08.014
Skog J, Würdinger T, van Rijn S et al (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10:1470–1476. https://doi.org/10.1038/ncb1800
Soares HD, Hicks RR, Smith D, McIntosh TK (1995) Inflammatory leukocytic recruitment and diffuse neuronal degeneration are separate pathological processes resulting from traumatic brain injury. J Neurosci 15:8223–8233. https://doi.org/10.1523/jneurosci.15-12-08223.1995
Spassky N, Merkle FT, Flames N et al (2005) Adult ependymal cells are postmitotic and are derived from radial glial cells during embryogenesis. J Neurosci 25:10–18. https://doi.org/10.1523/JNEUROSCI.1108-04.2005
Stence N, Waite M, Dailey ME (2001) Dynamics of microglial activation: a confocal time-lapse analysis in hippocampal slices. Glia 33:256–266. https://doi.org/10.1002/1098-1136(200103)33:3%3c256::AID-GLIA1024%3e3.0.CO;2-J
Streit WJ, Walter SA, Pennell NA (1999) Reactive microgliosis. Prog Neurobiol 57:563–581. https://doi.org/10.1016/S0301-0082(98)00069-0
Suvà ML, Tirosh I (2020) The glioma stem cell model in the era of single-cell genomics. Cancer Cell 37:630–636. https://doi.org/10.1016/j.ccell.2020.04.001
Tay TL, Mai D, Dautzenberg J et al (2017) A new fate mapping system reveals context-dependent random or clonal expansion of microglia. Nat Neurosci 20:793–803. https://doi.org/10.1038/nn.4547
Taylor CA, Bell JM, Breiding MJ, Xu L (2017) Traumatic brain injury-related emergency department visits, hospitalizations, and deaths—United States, 2007 and 2013. MMWR Surveill Summ 66:1–16. https://doi.org/10.15585/mmwr.ss6609a1
Van Hove H, Martens L, Scheyltjens I et al (2019) A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment. Nat Neurosci 22:1021–1035. https://doi.org/10.1038/s41593-019-0393-4
Wei J, Gabrusiewicz K, Heimberger A (2013) The controversial role of microglia in malignant gliomas. Clin Dev Immunol 2013:1–12. https://doi.org/10.1155/2013/285246
Wichterle H, Garcia-Verdugo JM, Herrera DG, Alvarez-Buylla A (1999) Young neurons from medial ganglionic eminence disperse in adult and embryonic brain. Nat Neurosci 2:461–466. https://doi.org/10.1038/8131
Wlodarczyk A, Holtman IR, Krueger M et al (2017) A novel microglial subset plays a key role in myelinogenesis in developing brain. EMBO J 36:3292–3308. https://doi.org/10.15252/embj.201696056
Xing C, Lo EH (2017) Help-me signaling: non-cell autonomous mechanisms of neuroprotection and neurorecovery. Prog Neurobiol 152:181–199
Yekula A, Minciacchi VR, Morello M et al (2019) Large and small extracellular vesicles released by glioma cells in vitro and in vivo. J Extracell Vesicles 9:1–10. https://doi.org/10.1080/20013078.2019.1689784
Zhan L, Sohn PD, Zhou Y et al (2020) A Mac2-positive progenitor-like microglial population survives independent of CSF1R signaling in adult mouse brain. Elife 9:1–22. https://doi.org/10.1101/722090
Zusso M, Methot L, Lo R et al (2012) Regulation of postnatal forebrain amoeboid microglial cell proliferation and development by the transcription factor Runx1. J Neurosci 32:11285–11298. https://doi.org/10.1523/JNEUROSCI.6182-11.2012
Funding
DMF has received support from National Institutes of Health, No. R15 NS096562/NS/NINDS NIH HHS/United States.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Ethical approval
This article does not contain any studies with human participants or animals performed by any of the authors.
Conflicts of interest
The authors declare no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Neckles, V.N., Feliciano, D.M. From seed to flower: blossoming of microglia in development and brain repair. Cell Tissue Res 387, 377–389 (2022). https://doi.org/10.1007/s00441-021-03486-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00441-021-03486-9