Top

Published in:

01-09-2017 | Original Paper

Microglia contribute to normal myelinogenesis and to oligodendrocyte progenitor maintenance during adulthood

Authors: Nora Hagemeyer, Klara-Maria Hanft, Maria-Anna Akriditou, Nicole Unger, Eun S. Park, E. Richard Stanley, Ori Staszewski, Leda Dimou, Marco Prinz

Published in: Acta Neuropathologica | Issue 3/2017

Abstract

Whereas microglia involvement in virtually all brain diseases is well accepted their role in the control of homeostasis in the central nervous system (CNS) is mainly thought to be the maintenance of neuronal function through the formation, refinement, and monitoring of synapses in both the developing and adult brain. Although the prenatal origin as well as the neuron-centered function of cortical microglia has recently been elucidated, much less is known about a distinct amoeboid microglia population formerly described as the “fountain of microglia” that appears only postnatally in myelinated regions such as corpus callosum and cerebellum. Using large-scale transcriptional profiling, fate mapping, and genetic targeting approaches, we identified a unique molecular signature of this microglia subset that arose from a CNS endogenous microglia pool independent from circulating myeloid cells. Microglia depletion experiments revealed an essential role of postnatal microglia for the proper development and homeostasis of oligodendrocytes and their progenitors. Our data provide new cellular and molecular insights into the myelin-supporting function of microglia in the normal CNS.

Available only for authorised users

Amit I, Winter DR, Jung S (2016) The role of the local environment and epigenetics in shaping macrophage identity and their effect on tissue homeostasis. Nat Immunol 17:18–25CrossRefPubMed

Banisadr G, Frederick TJ, Freitag C, Ren D, Jung H, Miller SD, Miller RJ (2011) The role of CXCR4 signaling in the migration of transplanted oligodendrocyte progenitors into the cerebral white matter. Neurobiol Dis 44:19–27. doi:10.1016/j.nbd.2011.05.019 PubMedPubMedCentral

Bruttger J, Karram K, Wörtge S, Regen T, Marini F, Hoppmann N, Klein M, Blank T, Yona S, Wolf Y, Mack M, Pinteaux E, Müller W, Zipp F, Binder H, Bopp T, Prinz M, Jung S, Waisman A (2015) Genetic cell ablation reveals clusters of local self-renewing microglia in the mammalian central nervous system. Immunity 43:92–106. doi:10.1016/j.immuni.2015.06.012 CrossRefPubMed

Butovsky O, Ziv Y, Schwartz A, Landa G, Talpalar AE, Pluchino S, Martino G, Schwartz M (2006) Microglia activated by IL-4 or IFN-γ differentially induce neurogenesis and oligodendrogenesis from adult stem/progenitor cells. Mol Cell Neurosci 31:149–160. doi:10.1016/j.mcn.2005.10.006 CrossRefPubMed

Chitu V, Gokhan S, Nandi S, Mehler MF, Stanley ER (2016) Emerging roles for CSF-1 receptor and its ligands in the nervous system. Trends Neurosci 39:378–393. doi:10.1016/j.tins.2016.03.005 CrossRefPubMedPubMedCentral

Colonna M, Butovsky O (2016) Microglia function in the central nervous system during health and neurodegeneration. Annu Rev Immunol. doi:10.1146/annurev-immunol-051116-052358

De Jager PL, Jia X, Wang J, de Bakker PIW, Ottoboni L, Aggarwal NT, Piccio L, Raychaudhuri S, Tran D, Aubin C, Briskin R, Romano S, Baranzini SE, McCauley JL, Pericak-Vance MA, Haines JL, Gibson RA, Naeglin Y, Uitdehaag B, Matthews PM, Kappos L, Polman C, McArdle WL, Strachan DP, Evans D, Cross AH, Daly MJ, Compston A, Sawcer SJ, Weiner HL, Hauser SL, Hafler DA, Oksenberg JR (2009) Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. Nat Genet 41:776–782. doi:10.1038/ng.401 CrossRefPubMedPubMedCentral

Elmore MRP, Najafi AR, Koike MA, Dagher NN, Spangenberg EE, Rice RA, Kitazawa M, Matusow B, Nguyen H, West BL, Green KN (2014) Colony-stimulating factor 1 receptor signaling is necessary for microglia viability, unmasking a microglia progenitor cell in the adult brain. Neuron 82:380–397. doi:10.1016/j.neuron.2014.02.040 CrossRefPubMedPubMedCentral

Ensan S, Li A, Besla R, Degousee N, Cosme J, Roufaiel M, Shikatani EA, El-Maklizi M, Williams JW, Robins L, Li C, Lewis B, Yun TJ, Lee JS, Wieghofer P, Khattar R, Farrokhi K, Byrne J, Ouzounian M, Zavitz CCJ, Levy GA, Bauer CMT, Libby P, Husain M, Swirski FK, Cheong C, Prinz M, Hilgendorf I, Randolph GJ, Epelman S, Gramolini AO, Cybulsky MI, Rubin BB, Robbins CS (2016) Self-renewing resident arterial macrophages arise from embryonic CX3CR1+ precursors and circulating monocytes immediately after birth. Nat Immunol 17:159–168CrossRefPubMed

10.

Erblich B, Zhu L, Etgen AM, Dobrenis K, Pollard JW (2011) Absence of colony stimulation factor-1 receptor results in loss of microglia, disrupted brain development and olfactory deficits. PLoS One 6:e26317. doi:10.1371/journal.pone.0026317 CrossRefPubMedPubMedCentral

11.

Erny D, Hrabe de Angelis AL, Jaitin D, Wieghofer P, Staszewski O, David E, Keren-Shaul H, Mahlakoiv T, Jakobshagen K, Buch T, Schwierzeck V, Utermohlen O, Chun E, Garrett WS, McCoy KD, Diefenbach A, Staeheli P, Stecher B, Amit I, Prinz M (2015) Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci 18:965–977CrossRefPubMedPubMedCentral

12.

Frank S, Burbach GJ, Bonin M, Walter M, Streit W, Bechmann I, Deller T (2008) TREM2 is upregulated in amyloid plaque-associated microglia in aged APP23 transgenic mice. Glia 56:1438–1447. doi:10.1002/glia.20710 CrossRefPubMed

13.

Ginhoux F, Greter M, Leboeuf M, Nandi S, See P, Gokhan S, Mehler MF, Conway SJ, Ng LG, Stanley ER, Samokhvalov IM, Merad M (2010) Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330:841–845. doi:10.1126/science.1194637 CrossRefPubMedPubMedCentral

14.

Goldmann T, Wieghofer P, Jordao MJC, Prutek F, Hagemeyer N, Frenzel K, Amann L, Staszewski O, Kierdorf K, Krueger M, Locatelli G, Hochgerner H, Zeiser R, Epelman S, Geissmann F, Priller J, Rossi FMV, Bechmann I, Kerschensteiner M, Linnarsson S, Jung S, Prinz M (2016) Origin, fate and dynamics of macrophages at central nervous system interfaces. Nat Immunol 17:797–805CrossRefPubMedPubMedCentral

15.

Goldmann T, Zeller N, Raasch J, Kierdorf K, Frenzel K, Ketscher L, Basters A, Staszewski O, Brendecke SM, Spiess A, Tay TL, Kreutz C, Timmer J, Mancini GM, Blank T, Fritz G, Biber K, Lang R, Malo D, Merkler D, Heikenwälder M, Knobeloch K-P, Prinz M (2015) USP18 lack in microglia causes destructive interferonopathy of the mouse brain. EMBO J 34:1612–1629. doi:10.15252/embj.201490791 CrossRefPubMedPubMedCentral

16.

Grabert K, Michoel T, Karavolos MH, Clohisey S, Baillie JK, Stevens MP, Freeman TC, Summers KM, McColl BW (2016) Microglial brain region-dependent diversity and selective regional sensitivities to aging. Nat Neurosci 19:504–516CrossRefPubMedPubMedCentral

17.

Griciuc A, Serrano-Pozo A, Parrado AR, Lesinski AN, Asselin CN, Mullin K, Hooli B, Choi SH, Hyman BT, Tanzi RE (2013) Alzheimer’s disease risk gene CD33 inhibits microglial uptake of amyloid beta. Neuron 78:631–643. doi:10.1016/j.neuron.2013.04.014 CrossRefPubMedPubMedCentral

18.

Guerreiro R, Wojtas A, Bras J, Carrasquillo M, Rogaeva E, Majounie E, Cruchaga C, Sassi C, Kauwe JSK, Younkin S, Hazrati L, Collinge J, Pocock J, Lashley T, Williams J, Lambert J-C, Amouyel P, Goate A, Rademakers R, Morgan K, Powell J, St. George-Hyslop P, Singleton A, Hardy J (2012) TREM2 Variants in Alzheimer’s Disease. N Engl J Med 368:117–127. doi:10.1056/NEJMoa1211851 CrossRefPubMedPubMedCentral

19.

Hagemeyer N, Goebbels S, Papiol S, Kästner A, Hofer S, Begemann M, Gerwig UC, Boretius S, Wieser GL, Ronnenberg A, Gurvich A, Heckers SH, Frahm J, Nave K-A, Ehrenreich H (2012) A myelin gene causative of a catatonia-depression syndrome upon aging. EMBO Mol Med 4:528–539. doi:10.1002/emmm.201200230 CrossRefPubMedPubMedCentral

20.

Hagemeyer N, Kierdorf K, Frenzel K, Xue J, Ringelhan M, Abdullah Z, Godin I, Wieghofer P, Costa Jordão MJ, Ulas T, Yorgancioglu G, Rosenbauer F, Knolle PA, Heikenwalder M, Schultze JL, Prinz M (2016) Transcriptome-based profiling of yolk sac-derived macrophages reveals a role for Irf8 in macrophage maturation. EMBO J 35:1730–1744. doi:10.15252/embj.201693801 CrossRefPubMedPubMedCentral

21.

Hickman SE, Kingery ND, Ohsumi T, Borowsky M, Wang L, Means TK, Khoury JE (2013) The microglial sensome revealed by direct RNA sequencing. Nat Neurosci 16:1896–1905. doi:10.1038/nn.3554 CrossRefPubMedPubMedCentral

22.

Hollingworth P, Harold D, Sims R, Gerrish A, Lambert J-C, Carrasquillo MM, Abraham R, Hamshere ML, Pahwa JS, Moskvina V, Dowzell K, Jones N, Stretton A, Thomas C, Richards A et al (2011) Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease. Nat Genet 43:429–435. doi:10.1038/ng.803 CrossRefPubMedPubMedCentral

23.

Holtman IR, Raj DD, Miller JA, Schaafsma W, Yin Z, Brouwer N, Wes PD, Möller T, Orre M, Kamphuis W, Hol EM, Boddeke EWGM, Eggen BJL (2015) Induction of a common microglia gene expression signature by aging and neurodegenerative conditions: a co-expression meta-analysis. Acta Neuropathol Commun 3:31. doi:10.1186/s40478-015-0203-5 CrossRefPubMedPubMedCentral

24.

Hristova M, Cuthill D, Zbarsky V, Acosta-Saltos A, Wallace A, Blight K, Buckley SMK, Peebles D, Heuer H, Waddington SN, Raivich G (2010) Activation and deactivation of periventricular white matter phagocytes during postnatal mouse development. Glia 58:11–28. doi:10.1002/glia.20896 CrossRefPubMed

25.

Imamoto K, Leblond CP (1978) Radioautographic investigation of gliogenesis in the corpus callosum of young rats II. Origin of microglial cells. J Comp Neurol 180:139–163. doi:10.1002/cne.901800109 CrossRefPubMed

26.

Jung S, Aliberti J, Graemmel P, Sunshine MJ, Kreutzberg GW, Sher A, Littman DR (2000) Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion. Mol Cell Biol 20:4106–4114CrossRefPubMedPubMedCentral

27.

Karram K, Goebbels S, Schwab M, Jennissen K, Seifert G, Steinhäuser C, Nave K-A, Trotter J (2008) NG2-expressing cells in the nervous system revealed by the NG2-EYFP-knockin mouse. Genesis 46:743–757. doi:10.1002/dvg.20440 CrossRefPubMed

28.

Kierdorf K, Erny D, Goldmann T, Sander V, Schulz C, Perdiguero EG, Wieghofer P, Heinrich A, Riemke P, Holscher C, Muller DN, Luckow B, Brocker T, Debowski K, Fritz G, Opdenakker G, Diefenbach A, Biber K, Heikenwalder M, Geissmann F, Rosenbauer F, Prinz M (2013) Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways. Nat Neurosci 16:273–280. doi:10.1038/nn.3318 CrossRefPubMed

29.

Kigerl KA, Gensel JC, Ankeny DP, Alexander JK, Donnelly DJ, Popovich PG (2009) Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci 29:13435. doi:10.1523/JNEUROSCI.3257-09.2009 CrossRefPubMedPubMedCentral

30.

Ling EA (1979) Transformation of monocytes into amoeboid microglia in the corpus callosum of postnatal rats, as shown by labelling monocytes by carbon particles. J Anat 128:847–858PubMedPubMedCentral

31.

Mason JL, Jones JJ, Taniike M, Morell P, Suzuki K, Matsushima GK (2000) Mature oligodendrocyte apoptosis precedes IGF-1 production and oligodendrocyte progenitor accumulation and differentiation during demyelination/remyelination. J Neurosci Res 61:251–262. doi:10.1002/1097-4547(20000801)61:3<251:AID-JNR3>3.0.CO;2-W CrossRefPubMed

32.

Matcovitch-Natan O, Winter DR, Giladi A, Vargas Aguilar S, Spinrad A, Sarrazin S, Ben-Yehuda H, David E, Zelada González F, Perrin P, Keren-Shaul H, Gury M, Lara-Astaiso D, Thaiss CA, Cohen M, Bahar Halpern K, Baruch K, Deczkowska A, Lorenzo-Vivas E, Itzkovitz S, Elinav E, Sieweke MH, Schwartz M, Amit I (2016) Microglia development follows a stepwise program to regulate brain homeostasis. Science. doi:10.1126/science.aad8670 PubMed

33.

Medzhitov R (2001) Toll-like receptors and innate immunity. Nat Rev Immunol 1:135–145. doi:10.1038/35100529 CrossRefPubMed

34.

Meuwissen MEC, Schot R, Buta S, Oudesluijs G, Tinschert S, Speer SD, Li Z, van Unen L, Heijsman D, Goldmann T, Lequin MH, Kros JM, Stam W, Hermann M, Willemsen R, Brouwer RWW, Van Ijcken WFJ, Martin-Fernandez M, de Coo I, Dudink J, de Vries FAT, Bertoli Avella A, Prinz M, Crow YJ, Verheijen FW, Pellegrini S, Bogunovic D, Mancini GMS (2016) Human USP18 deficiency underlies type 1 interferonopathy leading to severe pseudo-TORCH syndrome. J Exp Med 213:1163. doi:10.1084/jem.20151529 CrossRefPubMedPubMedCentral

35.

Mildner A, Mack M, Schmidt H, Brück W, Djukic M, Zabel MD, Hille A, Priller J, Prinz M (2009) CCR2⁺ Ly-6Chi monocytes are crucial for the effector phase of autoimmunity in the central nervous system. Brain 132:2487–2500. doi:10.1093/brain/awp144 CrossRefPubMed

36.

Mildner A, Schmidt H, Nitsche M, Merkler D, Hanisch U-K, Mack M, Heikenwalder M, Bruck W, Priller J, Prinz M (2007) Microglia in the adult brain arise from Ly-6ChiCCR2⁺ monocytes only under defined host conditions. Nat Neurosci 10:1544–1553. doi:10.1038/nn2015 CrossRefPubMed

37.

Miron VE, Boyd A, Zhao J-W, Yuen TJ, Ruckh JM, Shadrach JL, van Wijngaarden P, Wagers AJ, Williams A, Franklin RJ, ffrench-Constant C (2013) M2 microglia/macrophages drive oligodendrocyte differentiation during CNS remyelination. Nat Neurosci 16:1211–1218. doi:10.1038/nn.3469 CrossRefPubMedPubMedCentral

38.

Mizutani M, Pino PA, Saederup N, Charo IF, Ransohoff RM, Cardona AE (2011) The fractalkine receptor but not CCR2 is present on microglia from embryonic development throughout adulthood. J Immunol 188:29. doi:10.4049/jimmunol.1100421 CrossRefPubMedPubMedCentral

39.

Molawi K, Wolf Y, Kandalla PK, Favret J, Hagemeyer N, Frenzel K, Pinto AR, Klapproth K, Henri S, Malissen B, Rodewald H-R, Rosenthal NA, Bajenoff M, Prinz M, Jung S, Sieweke MH (2014) Progressive replacement of embryo-derived cardiac macrophages with age. J Exp Med 211:2151–2158. doi:10.1084/jem.20140639 CrossRefPubMedPubMedCentral

40.

Murtagh F, Legendre P (2014) Ward’s hierarchical agglomerative clustering method: which algorithms implement ward’s criterion? J Classif 31:274–295. doi:10.1007/s00357-014-9161-z CrossRef

41.

Naj AC, Jun G, Beecham GW, Wang L-S, Vardarajan BN, Buros J, Gallins PJ, Buxbaum JD, Jarvik GP, Crane PK, Larson EB, Bird TD, Boeve BF, Graff-Radford NR et al (2011) Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer’s disease. Nat Genet 43:436–441. doi:10.1038/ng.801 CrossRefPubMedPubMedCentral

42.

Nandi S, Gokhan S, Dai X-M, Wei S, Enikolopov G, Lin H, Mehler MF, Stanley ER (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. doi:10.1016/j.ydbio.2012.03.026 CrossRefPubMedPubMedCentral

43.

Nave K-A, Werner HB (2014) Myelination of the nervous system: mechanisms and functions. Annu Rev Cell Dev Biol 30:503–533. doi:10.1146/annurev-cellbio-100913-013101 CrossRefPubMed

44.

Paloneva J, Manninen T, Christman G, Hovanes K, Mandelin J, Adolfsson R, Bianchin M, Bird T, Miranda R, Salmaggi A, Tranebjærg L, Konttinen Y, Peltonen L (2002) Mutations in two genes encoding different subunits of a receptor signaling complex result in an identical disease phenotype. Am J Hum Genet 71:656–662. doi:10.1086/342259 CrossRefPubMedPubMedCentral

45.

Paolicelli RC, Bolasco G, Pagani F, Maggi L, Scianni M, Panzanelli P, Giustetto M, Ferreira TA, Guiducci E, Dumas L, Ragozzino D, Gross CT (2011) Synaptic pruning by microglia is necessary for normal brain development. Science 333:1456–1458. doi:10.1126/science.1202529 CrossRefPubMed

46.

Parkhurst CN, Yang G, Ninan I, Savas JN, Yates JR III, Lafaille JJ, Hempstead BL, Littman DR, Gan W-B (2013) Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell 155:1596–1609. doi:10.1016/j.cell.2013.11.030 CrossRefPubMedPubMedCentral

47.

Patel JR, McCandless EE, Dorsey D, Klein RS (2010) CXCR4 promotes differentiation of oligodendrocyte progenitors and remyelination. Proc Natl Acad Sci USA 107:11062–11067. doi:10.1073/pnas.1006301107 CrossRefPubMedPubMedCentral

48.

Peri F, Nüsslein-Volhard C (2008) Live imaging of neuronal degradation by microglia reveals a role for v0-ATPase a1 in phagosomal fusion in vivo. Cell 133:916–927. doi:10.1016/j.cell.2008.04.037 CrossRefPubMed

49.

Poggi G, Boretius S, Möbius W, Moschny N, Baudewig J, Ruhwedel T, Hassouna I, Wieser GL, Werner HB, Goebbels S, Nave K, Ehrenreich H (2016) Cortical network dysfunction caused by a subtle defect of myelination. Glia 64:2025–2040. doi:10.1002/glia.23039 CrossRefPubMedPubMedCentral

50.

Poliani PL, Wang Y, Fontana E, Robinette ML, Yamanishi Y, Gilfillan S, Colonna M (2015) TREM2 sustains microglial expansion during aging and response to demyelination. J Clin Invest 125:2161–2170. doi:10.1172/JCI77983 CrossRefPubMedPubMedCentral

51.

Prinz M, Erny D, Hagemeyer N (2017) Ontogeny and homeostasis of CNS myeloid cells. Nat Immunol 18:385CrossRefPubMed

52.

Prinz M, Priller J (2014) Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease. Nat Rev Neurosci 15:300–312. doi:10.1038/nrn3722 CrossRefPubMed

53.

Prinz M, Priller J (2017) The role of peripheral immune cells in the CNS in steady state and disease. Nat Neurosci 20:136–144CrossRefPubMed

54.

R Core Team R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna

55.

Rademakers R, Baker M, Nicholson AM, Rutherford NJ, Finch N, Soto-Ortolaza A, Lash J, Wider C, Wojtas A, DeJesus-Hernandez M, Adamson J, Kouri N, Sundal C, Shuster EA, Aasly J, MacKenzie J, Roeber S, Kretzschmar HA, Boeve BF, Knopman DS, Petersen RC, Cairns NJ, Ghetti B, Spina S, Garbern J, Tselis AC, Uitti R, Das P, Van Gerpen JA, Meschia JF, Levy S, Broderick DF, Graff-Radford N, Ross OA, Miller BB, Swerdlow RH, Dickson DW, Wszolek ZK (2012) Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids. Nat Genet 44:200–205. doi:10.1038/ng.1027 CrossRef

56.

Ransohoff RM, Perry Hugh H (2009) Microglial physiology: unique stimuli, specialized responses. Annu Rev Immunol 27:119–145. doi:10.1146/annurev.immunol.021908.132528 CrossRefPubMed

57.

Rezaie P, Dean A (2002) Periventricular leukomalacia, inflammation and white matter lesions within the developing nervous system. Neuropathology 22:106–132. doi:10.1046/j.1440-1789.2002.00438.x CrossRefPubMed

58.

Rio-Hortega P (1932) Microglia. Cytol Cell Pathol Nerv Syst 2:482–534

59.

Roumier A, Béchade C, Poncer J-C, Smalla K-H, Tomasello E, Vivier E, Gundelfinger ED, Triller A, Bessis A (2004) Impaired synaptic function in the microglial KARAP/DAP12-deficient mouse. J Neurosci 24:11421. doi:10.1523/JNEUROSCI.2251-04.2004 CrossRefPubMed

60.

Saederup N, Cardona AE, Croft K, Mizutani M, Cotleur AC, Tsou C-L, Ransohoff RM, Charo IF (2010) Selective chemokine receptor usage by central nervous system myeloid cells in CCR2-red fluorescent protein knock-in mice. PLoS One 5:e13693. doi:10.1371/journal.pone.0013693 CrossRefPubMedPubMedCentral

61.

Safaiyan S, Kannaiyan N, Snaidero N, Brioschi S, Biber K, Yona S, Edinger AL, Jung S, Rossner MJ, Simons M (2016) Age-related myelin degradation burdens the clearance function of microglia during aging. Nat Neurosci 19:995–998CrossRefPubMed

62.

Schafer DP, Lehrman EK, Kautzman AG, Koyama R, Mardinly AR, Yamasaki R, Ransohoff RM, Greenberg ME, Barres BA, Stevens B (2012) Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 74:691–705. doi:10.1016/j.neuron.2012.03.026 CrossRefPubMedPubMedCentral

63.

Scheffel J, Regen T, Van Rossum D, Seifert S, Ribes S, Nau R, Parsa R, Harris RA, Boddeke HWGM, Chuang H-N, Pukrop T, Wessels JT, Jürgens T, Merkler D, Brück W, Schnaars M, Simons M, Kettenmann H, Hanisch U-K (2012) Toll-like receptor activation reveals developmental reorganization and unmasks responder subsets of microglia. Glia 60:1930–1943. doi:10.1002/glia.22409 CrossRefPubMed

64.

Schulz C, Perdiguero EG, Chorro L, Szabo-Rogers H, Cagnard N, Kierdorf K, Prinz M, Wu B, Jacobsen SEW, Pollard JW, Frampton J, Liu KJ, Geissmann F (2012) A lineage of myeloid cells independent of Myb and hematopoietic stem cells. Science 336:86–90. doi:10.1126/science.1219179 CrossRefPubMed

65.

Shigemoto-Mogami Y, Hoshikawa K, Goldman JE, Sekino Y, Sato K (2014) Microglia enhance neurogenesis and oligodendrogenesis in the early postnatal subventricular zone. J Neurosci 34:2231–2243. doi:10.1523/JNEUROSCI.1619-13.2014 CrossRefPubMedPubMedCentral

66.

Sierra A, Encinas JM, Deudero JJP, Chancey JH, Enikolopov G, Overstreet-Wadiche LS, Tsirka SE, Maletic-Savatic M (2010) Microglia shape adult hippocampal neurogenesis through apoptosis-coupled phagocytosis. Cell Stem Cell 7:483–495. doi:10.1016/j.stem.2010.08.014 CrossRefPubMedPubMedCentral

67.

Simon C, Lickert H, Götz M, Dimou L (2012) Sox10-iCreERT2: a mouse line to inducibly trace the neural crest and oligodendrocyte lineage. Genesis 50:506–515. doi:10.1002/dvg.22003 CrossRefPubMed

68.

Skripuletz T, Miller E, Moharregh-Khiabani D, Blank A, Pul R, Gudi V, Trebst C, Stangel M (2010) Beneficial effects of minocycline on cuprizone induced cortical demyelination. Neurochem Res 35:1422–1433. doi:10.1007/s11064-010-0202-7 CrossRefPubMed

69.

Tremblay M-È, Lowery RL, Majewska AK (2010) Microglial interactions with synapses are modulated by visual experience. PLoS Biol 8:e1000527. doi:10.1371/journal.pbio.1000527 CrossRefPubMedPubMedCentral

70.

Ueno M, Fujita Y, Tanaka T, Nakamura Y, Kikuta J, Ishii M, Yamashita T (2013) Layer V cortical neurons require microglial support for survival during postnatal development. Nat Neurosci 16:543–551. doi:10.1038/nn.3358 CrossRefPubMed

71.

Viganò F, Schneider S, Cimino M, Bonfanti E, Gelosa P, Sironi L, Abbracchio MP, Dimou L (2016) GPR17 expressing NG2-Glia: oligodendrocyte progenitors serving as a reserve pool after injury. Glia 64:287–299. doi:10.1002/glia.22929 CrossRefPubMed

72.

Wake H, Moorhouse AJ, Jinno S, Kohsaka S, Nabekura J (2009) Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. J Neurosci 29:3974. doi:10.1523/JNEUROSCI.4363-08.2009 CrossRefPubMed

73.

Ward JH (1963) Hierarchical grouping to optimize an objective function. J Am Stat Assoc 69:236–244CrossRef

74.

Warnes GR, Bolker B, Bonebakker L, Gentleman R, Liaw WHA, Lumley T, Maechler M, Magnusson A, Moeller S, Schwartz M, Venables B (2016) gplots: various R programming tools for plotting data. R package version 3.0.1

75.

Zeger M, Popken G, Zhang J, Xuan S, Lu QR, Schwab MH, Nave K-A, Rowitch D, D’Ercole AJ, Ye P (2007) Insulin-like growth factor type 1 receptor signaling in the cells of oligodendrocyte lineage is required for normal in vivo oligodendrocyte development and myelination. Glia 55:400–411. doi:10.1002/glia.20469 CrossRefPubMedPubMedCentral

Title: Microglia contribute to normal myelinogenesis and to oligodendrocyte progenitor maintenance during adulthood
Authors: Nora Hagemeyer
Klara-Maria Hanft
Maria-Anna Akriditou
Nicole Unger
Eun S. Park
E. Richard Stanley
Ori Staszewski
Leda Dimou
Marco Prinz
Publication date: 01-09-2017
Publisher: Springer Berlin Heidelberg
Published in: Acta Neuropathologica / Issue 3/2017
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-017-1747-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Microglia contribute to normal myelinogenesis and to oligodendrocyte progenitor maintenance during adulthood

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2017

Phenotypic and functional characterization of T cells in white matter lesions of multiple sclerosis patients

Parietal white matter lesions in Alzheimer’s disease are associated with cortical neurodegenerative pathology, but not with small vessel disease

White matter injury in the preterm infant: pathology and mechanisms

H3-/IDH-wild type pediatric glioblastoma is comprised of molecularly and prognostically distinct subtypes with associated oncogenic drivers

Myelin regulatory factor drives remyelination in multiple sclerosis

Deleterious ABCA7 mutations and transcript rescue mechanisms in early onset Alzheimer’s disease