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Glial cells in neuronal development: recent advances and insights from Drosophila melanogaster

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Abstract

Glia outnumber neurons and are the most abundant cell type in the nervous system. Whereas neurons are the major carriers, transducers, and processors of information, glial cells, once considered mainly to play a passive supporting role, are now recognized for their active contributions to almost every aspect of nervous system development. Recently, insights from the invertebrate organism Drosophila melanogaster have advanced our knowledge of glial cell biology. In particular, findings on neuron-glia interactions via intrinsic and extrinsic mechanisms have shed light on the importance of glia during different stages of neuronal development. Here, we summarize recent advances in understanding the functions of Drosophila glia, which resemble their mammalian counterparts in morphology and function, neural stem-cell conversion, synapse formation, and developmental axon pruning. These discoveries reinforce the idea that glia are substantial players in the developing nervous system and further advance the understanding of mechanisms leading to neurodegeneration.

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References

  1. Chotard C, Salecker I. Neurons and glia: team players in axon guidance. Trends Neurosci 2004, 27: 655–661.

    Article  CAS  PubMed  Google Scholar 

  2. Bainton RJ, Tsai LT, Schwabe T, DeSalvo M, Gaul U, Heberlein U. moody encodes two GPCRs that regulate cocaine behaviors and blood-brain barrier permeability in Drosophila. Cell 2005, 123: 145–156.

    Article  CAS  PubMed  Google Scholar 

  3. Banerjee S, Pillai AM, Paik R, Li J, Bhat MA. Axonal ensheathment and septate junction formation in the peripheral nervous system of Drosophila. J Neurosci 2006, 26: 3319–3329.

    Article  CAS  PubMed  Google Scholar 

  4. Blauth K, Banerjee S, Bhat MA. Axonal ensheathment and intercellular barrier formation in Drosophila. Int Rev Cell Mol Biol 2010, 283: 93–128.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Stork T, Engelen D, Krudewig A, Silies M, Bainton RJ, Klambt C. Organization and function of the blood-brain barrier in Drosophila. J Neurosci 2008, 28: 587–597.

    Article  CAS  PubMed  Google Scholar 

  6. Araque A, Parpura V, Sanzgiri RP, Haydon PG. Tripartite synapses: glia, the unacknowledged partner. Trends Neurosci 1999, 22: 208–215.

    Article  CAS  PubMed  Google Scholar 

  7. Eroglu C, Barres BA. Regulation of synaptic connectivity by glia. Nature 2010, 468: 223–231.

    Article  CAS  PubMed  Google Scholar 

  8. Danjo R, Kawasaki F, Ordway RW. A tripartite synapse model in Drosophila. PLoS One 2011, 6: e17131.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Ransom HKaBR. Neuroglia. 3rd ed: Oxford University Press, 2013.

    Google Scholar 

  10. Coutinho-Budd J, Freeman MR. Probing the enigma: unraveling glial cell biology in invertebrates. Curr Opin Neurobiol 2013, 23: 1073–1079.

    Article  CAS  PubMed  Google Scholar 

  11. Barres BA. The mystery and magic of glia: a perspective on their roles in health and disease. Neuron 2008, 60: 430–440.

    Article  CAS  PubMed  Google Scholar 

  12. Corty MM, Freeman MR. Cell biology in neuroscience: Architects in neural circuit design: glia control neuron numbers and connectivity. J Cell Biol 2013, 203: 395–405.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Freeman MR, Doherty J. Glial cell biology in Drosophila and vertebrates. Trends Neurosci 2006, 29: 82–90.

    Article  CAS  PubMed  Google Scholar 

  14. Freeman MR, Rowitch DH. Evolving concepts of gliogenesis: a look way back and ahead to the next 25 years. Neuron 2013, 80: 613–623.

    Article  CAS  PubMed  Google Scholar 

  15. Edwards TN, Meinertzhagen IA. The functional organisation of glia in the adult brain of Drosophila and other insects. Prog Neurobiol 2010, 90: 471–497.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Hartenstein V. Morphological diversity and development of glia in Drosophila. Glia 2011, 59: 1237–1252.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Stork T, Bernardos R, Freeman MR. Analysis of glial cell development and function in Drosophila. Cold Spring Harb Protoc 2012, 2012: 1–17.

    Article  PubMed  Google Scholar 

  18. Poliak S, Peles E. The local differentiation of myelinated axons at nodes of Ranvier. Nat Rev Neurosci 2003, 4: 968–980.

    Article  CAS  PubMed  Google Scholar 

  19. Kurant E. Keeping the CNS clear: glial phagocytic functions in Drosophila. Glia 2011, 59: 1304–1311.

    Article  PubMed  Google Scholar 

  20. Logan MA, Freeman MR. The scoop on the fly brain: glial engulfment functions in Drosophila. Neuron Glia Biol 2007, 3: 63–74.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Homem CC, Knoblich JA. Drosophila neuroblasts: a model for stem cell biology. Development 2012, 139: 4297–4310.

    Article  CAS  PubMed  Google Scholar 

  22. Li X, Chen Z, Desplan C. Temporal patterning of neural progenitors in Drosophila. Curr Top Dev Biol 2013, 105: 69–96.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Maurange C. Temporal specification of neural stem cells: insights from Drosophila neuroblasts. Curr Top Dev Biol 2012, 98: 199–228.

    Article  PubMed  Google Scholar 

  24. Hartenstein V, Rudloff E, Campos-Ortega J. The pattern of proliferation of the neuroblasts in the wild-type embryo of Drosophila melanogaster. Roux’s archives of developmental biology 1987, 196: 473–485.

    Article  Google Scholar 

  25. Ito K, Hotta Y. Proliferation pattern of postembryonic neuroblasts in the brain of Drosophila melanogaster. Dev Biol 1992, 149: 134–148.

    Article  CAS  PubMed  Google Scholar 

  26. Prokop A, Technau GM. The origin of postembryonic neuroblasts in the ventral nerve cord of Drosophila melanogaster. Development 1991, 111: 79–88.

    CAS  PubMed  Google Scholar 

  27. Truman JW, Bate M. Spatial and temporal patterns of neurogenesis in the central nervous system of Drosophila melanogaster. Dev Biol 1988, 125: 145–157.

    Article  CAS  PubMed  Google Scholar 

  28. Bayraktar OA, Doe CQ. Combinatorial temporal patterning in progenitors expands neural diversity. Nature 2013, 498: 449–455.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Viktorin G, Riebli N, Reichert H. A multipotent transitamplifying neuroblast lineage in the central brain gives rise to optic lobe glial cells in Drosophila. Dev Biol 2013, 379: 182–194.

    Article  CAS  PubMed  Google Scholar 

  30. Wang YC, Yang JS, Johnston R, Ren Q, Lee YJ, Luan H, et al. Drosophila intermediate neural progenitors produce lineage-dependent related series of diverse neurons. Development 2014, 141: 253–258.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Hosoya T, Takizawa K, Nitta K, Hotta Y. Glial cells missing: a binary switch between neuronal and glial determination in Drosophila. Cell 1995, 82: 1025–1036.

    Article  CAS  PubMed  Google Scholar 

  32. Jones BW, Fetter RD, Tear G, Goodman CS. Glial cells missing: a genetic switch that controls glial versus neuronal fate. Cell 1995, 82: 1013–1023.

    Article  CAS  PubMed  Google Scholar 

  33. Vincent S, Vonesch JL, Giangrande A. Glide directs glial fate commitment and cell fate switch between neurones and glia. Development 1996, 122: 131–139.

    CAS  PubMed  Google Scholar 

  34. Viktorin G, Riebli N, Popkova A, Giangrande A, Reichert H. Multipotent neural stem cells generate glial cells of the central complex through transit amplifying intermediate progenitors in Drosophila brain development. Dev Biol 2011, 356: 553–565.

    Article  CAS  PubMed  Google Scholar 

  35. Flici H, Erkosar B, Komonyi O, Karatas OF, Laneve P, Giangrande A. Gcm/Glide-dependent conversion into glia depends on neural stem cell age, but not on division, triggering a chromatin signature that is conserved in vertebrate glia. Development 2011, 138: 4167–4178.

    Article  CAS  PubMed  Google Scholar 

  36. Hitoshi S, Ishino Y, Kumar A, Jasmine S, Tanaka KF, Kondo T, et al. Mammalian Gcm genes induce Hes5 expression by active DNA demethylation and induce neural stem cells. Nat Neurosci 2011, 14: 957–964.

    Article  CAS  PubMed  Google Scholar 

  37. Mao H, Lv Z, Ho MS. Gcm proteins function in the developing nervous system. Dev Biol 2012, 370: 63–70.

    Article  CAS  PubMed  Google Scholar 

  38. Chell JM, Brand AH. Nutrition-responsive glia control exit of neural stem cells from quiescence. Cell 2010, 143: 1161–1173.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Sousa-Nunes R, Yee LL, Gould AP. Fat cells reactivate quiescent neuroblasts via TOR and glial insulin relays in Drosophila. Nature 2011, 471: 508–512.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Goberdhan DC, Wilson C. The functions of insulin signaling: size isn’t everything, even in Drosophila. Differentiation 2003, 71: 375–397.

    Article  CAS  PubMed  Google Scholar 

  41. Ebens AJ, Garren H, Cheyette BN, Zipursky SL. The Drosophila anachronism locus: a glycoprotein secreted by glia inhibits neuroblast proliferation. Cell 1993, 74: 15–27.

    Article  CAS  PubMed  Google Scholar 

  42. Friedrich MV, Schneider M, Timpl R, Baumgartner S. Perlecan domain V of Drosophila melanogaster. Sequence, recombinant analysis and tissue expression. Eur J Biochem 2000, 267: 3149–3159.

    Article  CAS  PubMed  Google Scholar 

  43. Lindner JR, Hillman PR, Barrett AL, Jackson MC, Perry TL, Park Y, et al. The Drosophila Perlecan gene trol regulates multiple signaling pathways in different developmental contexts. BMC Dev Biol 2007, 7: 121.

    Article  PubMed Central  PubMed  Google Scholar 

  44. Voigt A, Pflanz R, Schafer U, Jackle H. Perlecan participates in proliferation activation of quiescent Drosophila neuroblasts. Dev Dyn 2002, 224: 403–412.

    Article  CAS  PubMed  Google Scholar 

  45. Callan MA, Clements N, Ahrendt N, Zarnescu DC. Fragile X Protein is required for inhibition of insulin signaling and regulates glial-dependent neuroblast reactivation in the developing brain. Brain Res 2012, 1462: 151–161.

    Article  CAS  PubMed  Google Scholar 

  46. Brummel T, Abdollah S, Haerry TE, Shimell MJ, Merriam J, Raftery L, et al. The Drosophila activin receptor baboon signals through dSmad2 and controls cell proliferation but not patterning during larval development. Genes Dev 1999, 13: 98–111.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Zhu CC, Boone JQ, Jensen PA, Hanna S, Podemski L, Locke J, et al. Drosophila Activin- and the Activin-like product Dawdle function redundantly to regulate proliferation in the larval brain. Development 2008, 135: 513–521.

    Article  CAS  PubMed  Google Scholar 

  48. Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008, 133: 704–715.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Morante J, Vallejo DM, Desplan C, Dominguez M. Conserved miR-8/miR-200 defines a glial niche that controls neuroepithelial expansion and neuroblast transition. Dev Cell 2013, 27: 174–187.

    Article  CAS  PubMed  Google Scholar 

  50. Menon KP, Carrillo RA, Zinn K. Development and plasticity of the Drosophila larval neuromuscular junction. Wiley Interdiscip Rev Dev Biol 2013, 2: 647–670.

    Article  CAS  PubMed  Google Scholar 

  51. Ruiz-Canada C, Budnik V. Introduction on the use of the Drosophila embryonic/larval neuromuscular junction as a model system to study synapse development and function, and a brief summary of pathfinding and target recognition. Int Rev Neurobiol 2006, 75: 1–31.

    Article  CAS  PubMed  Google Scholar 

  52. Fuentes-Medel Y, Ashley J, Barria R, Maloney R, Freeman M, Budnik V. Integration of a retrograde signal during synapse formation by glia-secreted TGF-beta ligand. Curr Biol 2012, 22: 1831–1838.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Fuentes-Medel Y, Logan MA, Ashley J, Ataman B, Budnik V, Freeman MR. Glia and muscle sculpt neuromuscular arbors by engulfing destabilized synaptic boutons and shed presynaptic debris. PLoS Biol 2009, 7: e1000184.

    Article  PubMed Central  PubMed  Google Scholar 

  54. Keller LC, Cheng L, Locke CJ, Muller M, Fetter RD, Davis GW. Glial-derived prodegenerative signaling in the Drosophila neuromuscular system. Neuron 2011, 72: 760–775.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. Kerr KS, Fuentes-Medel Y, Brewer C, Barria R, Ashley J, Abruzzi KC, et al. Glial wingless/wnt regulates glutamate receptor clustering and synaptic physiology at the Drosophila neuromuscular junction. J Neurosci 2014, 34: 2910–2920.

    Article  CAS  PubMed  Google Scholar 

  56. Brink DL, Gilbert M, Xie X, Petley-Ragan L, Auld VJ. Glial processes at the Drosophila larval neuromuscular junction match synaptic growth. PLoS One 2012, 7: e37876.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  57. Brink D, Gilbert M, Auld V. Visualizing the live Drosophila glial-neuromuscular junction with fluorescent dyes. J Vis Exp 2009, pii: 1154.

    Google Scholar 

  58. Ataman B, Ashley J, Gorczyca D, Gorczyca M, Mathew D, Wichmann C, et al. Nuclear trafficking of Drosophila Frizzled-2 during synapse development requires the PDZ protein dGRIP. Proc Natl Acad Sci U S A 2006, 103: 7841–7846.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  59. Mathew D, Ataman B, Chen J, Zhang Y, Cumberledge S, Budnik V. Wingless signaling at synapses is through cleavage and nuclear import of receptor DFrizzled2. Science 2005, 310: 1344–1347.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  60. Miech C, Pauer HU, He X, Schwarz TL. Presynaptic local signaling by a canonical wingless pathway regulates development of the Drosophila neuromuscular junction. J Neurosci 2008, 28: 10875–10884.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Packard M, Koo ES, Gorczyca M, Sharpe J, Cumberledge S, Budnik V. The Drosophila Wnt, wingless, provides an essential signal for pre- and postsynaptic differentiation. Cell 2002, 111: 319–330.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Ball RW, Warren-Paquin M, Tsurudome K, Liao EH, Elazzouzi F, Cavanagh C, et al. Retrograde BMP signaling controls synaptic growth at the NMJ by regulating trio expression in motor neurons. Neuron 2010, 66: 536–549.

    Article  CAS  PubMed  Google Scholar 

  63. Fuentes-Medel Y, Budnik V. Menage a Trio during BMPmediated retrograde signaling at the NMJ. Neuron 2010, 66: 473–475.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  64. Pielage J, Cheng L, Fetter RD, Carlton PM, Sedat JW, Davis GW. A presynaptic giant ankyrin stabilizes the NMJ through regulation of presynaptic microtubules and transsynaptic cell adhesion. Neuron 2008, 58: 195–209.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  65. Pielage J, Fetter RD, Davis GW. Presynaptic spectrin is essential for synapse stabilization. Curr Biol 2005, 15: 918–928.

    Article  CAS  PubMed  Google Scholar 

  66. Massaro CM, Pielage J, Davis GW. Molecular mechanisms that enhance synapse stability despite persistent disruption of the spectrin/ankyrin/microtubule cytoskeleton. J Cell Biol 2009, 187: 101–117.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  67. Ataman B, Ashley J, Gorczyca M, Ramachandran P, Fouquet W, Sigrist SJ, et al. Rapid activity-dependent modifications in synaptic structure and function require bidirectional Wnt signaling. Neuron 2008, 57: 705–718.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  68. Lee T, Marticke S, Sung C, Robinow S, Luo L. Cellautonomous requirement of the USP/EcR-B ecdysone receptor for mushroom body neuronal remodeling in Drosophila. Neuron 2000, 28: 807–818.

    Article  CAS  PubMed  Google Scholar 

  69. Watts RJ, Hoopfer ED, Luo L. Axon pruning during Drosophila metamorphosis: evidence for local degeneration and requirement of the ubiquitin-proteasome system. Neuron 2003, 38: 871–885.

    Article  CAS  PubMed  Google Scholar 

  70. Awasaki T, Huang Y, O’Connor MB, Lee T. Glia instruct developmental neuronal remodeling through TGF-beta signaling. Nat Neurosci 2011, 14: 821–823.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  71. Yu XM, Gutman I, Mosca TJ, Iram T, Ozkan E, Garcia KC, et al. Plum, an immunoglobulin superfamily protein, regulates axon pruning by facilitating TGF-beta signaling. Neuron 2013, 78: 456–468.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  72. Awasaki T, Ito K. Engulfing action of glial cells is required for programmed axon pruning during Drosophila metamorphosis. Curr Biol 2004, 14: 668–677.

    Article  CAS  PubMed  Google Scholar 

  73. Awasaki T, Tatsumi R, Takahashi K, Arai K, Nakanishi Y, Ueda R, et al. Essential role of the apoptotic cell engulfment genes draper and ced-6 in programmed axon pruning during Drosophila metamorphosis. Neuron 2006, 50: 855–867.

    Article  CAS  PubMed  Google Scholar 

  74. Watts RJ, Schuldiner O, Perrino J, Larsen C, Luo L. Glia engulf degenerating axons during developmental axon pruning. Curr Biol 2004, 14: 678–684.

    Article  CAS  PubMed  Google Scholar 

  75. Hakim Y, Yaniv SP, Schuldiner O. Astrocytes play a key role in Drosophila mushroom body axon pruning. PLoS One 2014, 9: e86178.

    Article  PubMed Central  PubMed  Google Scholar 

  76. Freeman MR, Delrow J, Kim J, Johnson E, Doe CQ. Unwrapping glial biology: Gcm target genes regulating glial development, diversification, and function. Neuron 2003, 38: 567–580.

    Article  CAS  PubMed  Google Scholar 

  77. Kurant E, Axelrod S, Leaman D, Gaul U. Six-microns-under acts upstream of Draper in the glial phagocytosis of apoptotic neurons. Cell 2008, 133: 498–509.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  78. Hoopfer ED, McLaughlin T, Watts RJ, Schuldiner O, O’Leary DD, Luo L. Wlds protection distinguishes axon degeneration following injury from naturally occurring developmental pruning. Neuron 2006, 50: 883–895.

    Article  CAS  PubMed  Google Scholar 

  79. MacDonald JM, Beach MG, Porpiglia E, Sheehan AE, Watts RJ, Freeman MR. The Drosophila cell corpse engulfment receptor Draper mediates glial clearance of severed axons. Neuron 2006, 50: 869–881.

    Article  CAS  PubMed  Google Scholar 

  80. Logan MA, Hackett R, Doherty J, Sheehan A, Speese SD, Freeman MR. Negative regulation of glial engulfment activity by Draper terminates glial responses to axon injury. Nat Neurosci 2012, 15: 722–730.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  81. Ziegenfuss JS, Biswas R, Avery MA, Hong K, Sheehan AE, Yeung YG, et al. Draper-dependent glial phagocytic activity is mediated by Src and Syk family kinase signalling. Nature 2008, 453: 935–939.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  82. Ziegenfuss JS, Doherty J, Freeman MR. Distinct molecular pathways mediate glial activation and engulfment of axonal debris after axotomy. Nat Neurosci 2012, 15: 979–987.

    Article  CAS  PubMed  Google Scholar 

  83. Tasdemir-Yilmaz OE, Freeman MR. Astrocytes engage unique molecular programs to engulf pruned neuronal debris from distinct subsets of neurons. Genes Dev 2014, 28: 20–33.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  84. Doherty J, Logan MA, Tasdemir OE, Freeman MR. Ensheathing glia function as phagocytes in the adult Drosophila brain. J Neurosci 2009, 29: 4768–4781.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Anatomy and Neurobiology, School of Medicine, Tongji University, Shanghai, 200092, China

    Jiayao Ou, Yijing He, Xi Xiao, Tian-Ming Yu, Zongbao Gao & Margaret S. Ho

  2. School of Life Sciences, Tongji University, Shanghai, 200092, China

    Changyan Chen

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  1. Jiayao Ou
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  2. Yijing He
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  3. Xi Xiao
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  7. Margaret S. Ho
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Correspondence to Margaret S. Ho.

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Ou, J., He, Y., Xiao, X. et al. Glial cells in neuronal development: recent advances and insights from Drosophila melanogaster . Neurosci. Bull. 30, 584–594 (2014). https://doi.org/10.1007/s12264-014-1448-2

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