Regulation of Subventricular Zone-Derived Cells Migration in the Adult Brain

  • Vivian Capilla-Gonzalez
  • Emily Lavell
  • Alfredo Quiñones-Hinojosa
  • Hugo Guerrero-CazaresEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 853)


The subventricular zone of the lateral ventricles (SVZ) is the largest source of neural stem cells (NSCs) in the adult mammalian brain. Newly generated neuroblasts from the SVZ form cellular chains that migrate through the rostral migratory stream (RMS) into the olfactory bulb (OB), where they become mature neurons. Migration through the RMS is a highly regulated process of intrinsic and extrinsic factors, orchestrated to achieve direction and integration of neuroblasts into OB circuitry. These factors include internal cytoskeletal and volume regulators, extracellular matrix proteins, and chemoattractant and chemorepellent proteins. All these molecules direct the cells away from the SVZ, through the RMS, and into the OB guaranteeing their correct integration. Following brain injury, some neuroblasts escape the RMS and migrate into the lesion site to participate in regeneration, a phenomenon that is also observed with brain tumors. This review focuses on factors that regulate the migration of SVZ precursor cells in the healthy and pathologic brain. A better understanding of the factors that control the movement of newly generated cells may be crucial for improving the use of NSC-replacement therapy for specific neurological diseases.


Neural stem cells Subventricular zone Rostral migratory stream Neuroblasts Neuronal migration Regulation of migration Adult neurogenesis Brain tumors 


  1. 1.
    Johansson CB, Momma S, Clarke DL, Risling M, Lendahl U, Frisen J. Identification of a neural stem cell in the adult mammalian central nervous system. Cell. 1999;96(1):25–34. doi: 10.1016/s0092-8674(00)80956-3.PubMedGoogle Scholar
  2. 2.
    Doetsch F, Garcia-Verdugo JM, Alvarez-Buylla A. Regeneration of a germinal layer in the adult mammalian brain. Proc Natl Acad Sci U S A. 1999;96(20):11619–24.PubMedCentralPubMedGoogle Scholar
  3. 3.
    Ponti G, Obernier K, Guinto C, Jose L, Bonfanti L, Alvarez-Buylla A. Cell cycle and lineage progression of neural progenitors in the ventricular-subventricular zones of adult mice. Proc Natl Acad Sci U S A. 2013;110(11):E1045–54. doi: 10.1073/pnas.1219563110. 1219563110 [pii].PubMedCentralPubMedGoogle Scholar
  4. 4.
    Luskin MB, Zigova T, Soteres BJ, Stewart RR. Neuronal progenitor cells derived from the anterior subventricular zone of the neonatal rat forebrain continue to proliferate in vitro and express a neuronal phenotype. Mol Cell Neurosci. 1997;8(5):351–66. doi: 10.1006/mcne.1996.0592. S1044-7431(96)90592-8 [pii].PubMedGoogle Scholar
  5. 5.
    Lazarini F, Lledo PM. Is adult neurogenesis essential for olfaction? Trends Neurosci. 2011;34(1):20–30. doi: 10.1016/j.tins.2010.09.006. S0166-2236(10)00137-2 [pii].PubMedGoogle Scholar
  6. 6.
    Imayoshi I, Sakamoto M, Ohtsuka T, Takao K, Miyakawa T, Yamaguchi M, Mori K, Ikeda T, Itohara S, Kageyama R. Roles of continuous neurogenesis in the structural and functional integrity of the adult forebrain. Nat Neurosci. 2008;11(10):1153–61.PubMedGoogle Scholar
  7. 7.
    Lois C, Garcia-Verdugo JM, Alvarez-Buylla A. Chain migration of neuronal precursors. Science. 1996;271(5251):978–81.PubMedGoogle Scholar
  8. 8.
    Carleton A, Petreanu LT, Lansford R, Alvarez-Buylla A, Lledo PM. Becoming a new neuron in the adult olfactory bulb. Nat Neurosci. 2003;6(5):507–18. doi: 10.1038/nn1048.PubMedGoogle Scholar
  9. 9.
    Capilla-Gonzalez V, Cebrian-Silla A, Guerrero-Cazares H, Garcia-Verdugo JM, Quinones-Hinojosa A. The generation of oligodendroglial cells is preserved in the rostral migratory stream during aging. Front Cell Neurosci. 2013;7:147. doi: 10.3389/fncel.2013.00147.PubMedCentralPubMedGoogle Scholar
  10. 10.
    Lois C, Alvarez-Buylla A. Long-distance neuronal migration in the adult mammalian brain. Science. 1994;264(5162):1145–8.PubMedGoogle Scholar
  11. 11.
    Belvindrah R, Lazarini F, Lledo PM. Postnatal neurogenesis: from neuroblast migration to neuronal integration. Rev Neurosci. 2009;20(5–6):331–46.PubMedGoogle Scholar
  12. 12.
    Lledo PM, Alonso M, Grubb MS. Adult neurogenesis and functional plasticity in neuronal circuits. Nat Rev Neurosci. 2006;7(3):179–93. doi: 10.1038/nrn1867. nrn1867 [pii].PubMedGoogle Scholar
  13. 13.
    Petreanu L, Alvarez-Buylla A. Maturation and death of adult-born olfactory bulb granule neurons: role of olfaction. J Neurosci. 2002;22(14):6106–13.PubMedGoogle Scholar
  14. 14.
    Capilla-Gonzalez V, Gil-Perotin S, Ferragud A, Bonet-Ponce L, Canales JJ, Garcia-Verdugo JM. Exposure to N-ethyl-N-nitrosourea in adult mice alters structural and functional integrity of neurogenic sites. PLoS One. 2012;7(1):e29891. doi: 10.1371/journal.pone.0029891. PONE-D-11-07990 [pii].PubMedCentralPubMedGoogle Scholar
  15. 15.
    Sanai N, Berger MS, Garcia-Verdugo JM, Alvarez-Buylla A. Comment on “Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension”. Science. 2007;318(5849):393. doi: 10.1126/science.1145011. 318/5849/393b [pii].PubMedGoogle Scholar
  16. 16.
    Curtis MA, Kam M, Nannmark U, Anderson MF, Axell MZ, Wikkelso C, Holtas S, van Roon-Mom WM, Bjork-Eriksson T, Nordborg C, Frisen J, Dragunow M, Faull RL, Eriksson PS. Human neuroblasts migrate to the olfactory bulb via a lateral ventricular extension. Science. 2007;315(5816):1243–9. doi: 10.1126/science.1136281. 1136281 [pii].PubMedGoogle Scholar
  17. 17.
    Wang C, Liu F, Liu YY, Zhao CH, You Y, Wang L, Zhang J, Wei B, Ma T, Zhang Q, Zhang Y, Chen R, Song H, Yang Z. Identification and characterization of neuroblasts in the subventricular zone and rostral migratory stream of the adult human brain. Cell Res. 2011;21(11):1534–50. doi: 10.1038/cr.2011.83. cr201183 [pii].PubMedCentralPubMedGoogle Scholar
  18. 18.
    Kam M, Curtis MA, McGlashan SR, Connor B, Nannmark U, Faull RL. The cellular composition and morphological organization of the rostral migratory stream in the adult human brain. J Chem Neuroanat. 2009;37(3):196–205. doi: 10.1016/j.jchemneu.2008.12.009. S0891-0618(08)00165-8 [pii].PubMedGoogle Scholar
  19. 19.
    Sanai N, Tramontin AD, Quinones-Hinojosa A, Barbaro NM, Gupta N, Kunwar S, Lawton MT, McDermott MW, Parsa AT, Garcia-Verdugo JM, Berger MS, Alvarez-Buylla A. Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration. Nature. 2004;427(6976):740–4. doi: 10.1038/nature02301. nature02301 [pii].PubMedGoogle Scholar
  20. 20.
    Guerrero-Cazares H, Gonzalez-Perez O, Soriano-Navarro M, Zamora-Berridi G, Garcia-Verdugo JM, Quinones-Hinojosa A. Cytoarchitecture of the lateral ganglionic eminence and rostral extension of the lateral ventricle in the human fetal brain. J Comp Neurol. 2011;519(6):1165–80. doi: 10.1002/cne.22566.PubMedGoogle Scholar
  21. 21.
    Quinones-Hinojosa A, Sanai N, Soriano-Navarro M, Gonzalez-Perez O, Mirzadeh Z, Gil-Perotin S, Romero-Rodriguez R, Berger MS, Garcia-Verdugo JM, Alvarez-Buylla A. Cellular composition and cytoarchitecture of the adult human subventricular zone: a niche of neural stem cells. J Comp Neurol. 2006;494(3):415–34. doi: 10.1002/cne.20798.PubMedGoogle Scholar
  22. 22.
    Sanai N, Nguyen T, Ihrie RA, Mirzadeh Z, Tsai HH, Wong M, Gupta N, Berger MS, Huang E, Garcia-Verdugo JM, Rowitch DH, Alvarez-Buylla A. Corridors of migrating neurons in the human brain and their decline during infancy. Nature. 2011;478(7369):382–6. doi: 10.1038/nature10487. nature10487 [pii].PubMedCentralPubMedGoogle Scholar
  23. 23.
    Kaneko N, Marin O, Koike M, Hirota Y, Uchiyama Y, Wu JY, Lu Q, Tessier-Lavigne M, Alvarez-Buylla A, Okano H, Rubenstein JL, Sawamoto K. New neurons clear the path of astrocytic processes for their rapid migration in the adult brain. Neuron. 2010;67(2):213–23. doi: 10.1016/j.neuron.2010.06.018.PubMedCentralPubMedGoogle Scholar
  24. 24.
    Sawamoto K, Wichterle H, Gonzalez-Perez O, Cholfin JA, Yamada M, Spassky N, Murcia NS, Garcia-Verdugo JM, Marin O, Rubenstein JL, Tessier-Lavigne M, Okano H, Alvarez-Buylla A. New neurons follow the flow of cerebrospinal fluid in the adult brain. Science. 2006;311(5761):629–32.PubMedGoogle Scholar
  25. 25.
    Vukovic J, Blackmore DG, Jhaveri D, Bartlett PF. Activation of neural precursors in the adult neurogenic niches. Neurochem Int. 2011;59(3):341–6. doi: 10.1016/j.neuint.2011.04.003. S0197-0186(11)00156-2 [pii].PubMedGoogle Scholar
  26. 26.
    Christie KJ, Turnley AM. Regulation of endogenous neural stem/progenitor cells for neural repair-factors that promote neurogenesis and gliogenesis in the normal and damaged brain. Front Cell Neurosci. 2012;6:70. doi: 10.3389/fncel.2012.00070.PubMedCentralPubMedGoogle Scholar
  27. 27.
    Nait-Oumesmar B, Decker L, Lachapelle F, Avellana-Adalid V, Bachelin C, Van Evercooren AB. Progenitor cells of the adult mouse subventricular zone proliferate, migrate and differentiate into oligodendrocytes after demyelination. Eur J Neurosci. 1999;11(12):4357–66. doi:ejn873 [pii].PubMedGoogle Scholar
  28. 28.
    Marti-Fabregas J, Romaguera-Ros M, Gomez-Pinedo U, Martinez-Ramirez S, Jimenez-Xarrie E, Marin R, Marti-Vilalta JL, Garcia-Verdugo JM. Proliferation in the human ipsilateral subventricular zone after ischemic stroke. Neurology. 2010;74(5):357–65. doi: 10.1212/WNL.0b013e3181cbccec. WNL.0b013e3181cbccec [pii].PubMedGoogle Scholar
  29. 29.
    Yamashita T, Ninomiya M, Hernandez Acosta P, Garcia-Verdugo JM, Sunabori T, Sakaguchi M, Adachi K, Kojima T, Hirota Y, Kawase T, Araki N, Abe K, Okano H, Sawamoto K. Subventricular zone-derived neuroblasts migrate and differentiate into mature neurons in the post-stroke adult striatum. J Neurosci. 2006;26(24):6627–36.PubMedGoogle Scholar
  30. 30.
    Barkho BZ, Zhao X. Adult neural stem cells: response to stroke injury and potential for therapeutic applications. Curr Stem Cell Res Ther. 2011;6(4):327–38. doi:BSP/CSCRT/E-Pub/00090 [pii].PubMedCentralPubMedGoogle Scholar
  31. 31.
    Capilla-Gonzalez V, Guerrero-Cazares H, Bonsu JM, Gonzalez-Perez O, Achanta P, Wong J, Garcia-Verdugo JM, Quinones-Hinojosa A. The subventricular zone is able to respond to a demyelinating lesion after localized radiation. Stem Cells. 2014;32(1):59–69. doi: 10.1002/stem.1519.PubMedGoogle Scholar
  32. 32.
    Doetsch F, Caille I, Lim DA, Garcia-Verdugo JM, Alvarez-Buylla A. Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell. 1999;97(6):703–16.PubMedGoogle Scholar
  33. 33.
    Ihrie RA, Alvarez-Buylla A. Cells in the astroglial lineage are neural stem cells. Cell Tissue Res. 2008;331(1):179–91. doi: 10.1007/s00441-007-0461-z.PubMedGoogle Scholar
  34. 34.
    Morrens J, Van Den Broeck W, Kempermann G. Glial cells in adult neurogenesis. Glia. 2012;60(2):159–74. doi: 10.1002/glia.21247.PubMedGoogle Scholar
  35. 35.
    Doetsch F, Garcia-Verdugo JM, Alvarez-Buylla A. Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J Neurosci. 1997;17(13):5046–61.PubMedGoogle Scholar
  36. 36.
    Han YG, Spassky N, Romaguera-Ros M, Garcia-Verdugo JM, Aguilar A, Schneider-Maunoury S, Alvarez-Buylla A. Hedgehog signaling and primary cilia are required for the formation of adult neural stem cells. Nat Neurosci. 2008;11(3):277–84. doi: 10.1038/nn2059. nn2059 [pii].PubMedGoogle Scholar
  37. 37.
    Mirzadeh Z, Merkle FT, Soriano-Navarro M, Garcia-Verdugo JM, Alvarez-Buylla A. Neural stem cells confer unique pinwheel architecture to the ventricular surface in neurogenic regions of the adult brain. Cell Stem Cell. 2008;3(3):265–78.PubMedCentralPubMedGoogle Scholar
  38. 38.
    Gil-Perotin S, Alvarez-Buylla A, Garcia-Verdugo JM. Identification and characterization of neural progenitor cells in the adult mammalian brain. Adv Anat Embryol Cell Biol. 2009;203:1–101. ix.PubMedGoogle Scholar
  39. 39.
    Ming GL, Song HJ. Adult neurogenesis in the mammalian central nervous system. Annu Rev Neurosci. 2005;28:223–50. doi: 10.1146/annurev.neuro.28.051804.101459.PubMedGoogle Scholar
  40. 40.
    Gleeson JG, Lin PT, Flanagan LA, Walsh CA. Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons. Neuron. 1999;23(2):257–71.PubMedGoogle Scholar
  41. 41.
    Didier M, Harandi M, Aguera M, Bancel B, Tardy M, Fages C, Calas A, Stagaard M, Mollgard K, Belin MF. Differential immunocytochemical staining for glial fibrillary acidic (GFA) protein, S-100 protein and glutamine synthetase in the rat subcommissural organ, nonspecialized ventricular ependyma and adjacent neuropil. Cell Tissue Res. 1986;245(2):343–51.PubMedGoogle Scholar
  42. 42.
    Craig CG, Tropepe V, Morshead CM, Reynolds BA, Weiss S, van der Kooy D. In vivo growth factor expansion of endogenous subependymal neural precursor cell populations in the adult mouse brain. J Neurosci. 1996;16(8):2649–58.PubMedGoogle Scholar
  43. 43.
    Spassky N, Merkle FT, Flames N, Tramontin AD, Garcia-Verdugo JM, Alvarez-Buylla A. Adult ependymal cells are postmitotic and are derived from radial glial cells during embryogenesis. J Neurosci. 2005;25(1):10–8.PubMedGoogle Scholar
  44. 44.
    Alvarez-Buylla A, Garcia-Verdugo JM. Neurogenesis in adult subventricular zone. J Neurosci. 2002;22(3):629–34.PubMedGoogle Scholar
  45. 45.
    Peretto P, Merighi A, Fasolo A, Bonfanti L. Glial tubes in the rostral migratory stream of the adult rat. Brain Res Bull. 1997;42(1):9–21. doi:S0361-9230(96)00116-5 [pii].PubMedGoogle Scholar
  46. 46.
    Pencea V, Bingaman KD, Freedman LJ, Luskin MB. Neurogenesis in the subventricular zone and rostral migratory stream of the neonatal and adult primate forebrain. Exp Neurol. 2001;172(1):1–16. doi: 10.1006/exnr.2001.7768.PubMedGoogle Scholar
  47. 47.
    De Marchis S, Fasolo A, Puche AC. Subventricular zone-derived neuronal progenitors migrate into the subcortical forebrain of postnatal mice. J Comp Neurol. 2004;476(3):290–300. doi: 10.1002/cne.20217.PubMedGoogle Scholar
  48. 48.
    Sawada M, Sawamoto K. Mechanisms of neurogenesis in the normal and injured adult brain. Keio J Med. 2013;62(1):13–28.PubMedGoogle Scholar
  49. 49.
    Porlan E, Perez-Villalba A, Delgado AC, Ferron SR. Paracrine regulation of neural stem cells in the subependymal zone. Arch Biochem Biophys. 2013;534(1–2):11–9. doi: 10.1016/ S0003-9861(12)00360-8 [pii].PubMedGoogle Scholar
  50. 50.
    Pencea V, Luskin MB. Prenatal development of the rodent rostral migratory stream. J Comp Neurol. 2003;463(4):402–18. doi: 10.1002/cne.10746.PubMedGoogle Scholar
  51. 51.
    Mobley AS, Bryant AK, Richard MB, Brann JH, Firestein SJ, Greer CA. Age-dependent regional changes in the rostral migratory stream. Neurobiol Aging. 2013;34(7):1873–81. doi: 10.1016/j.neurobiolaging.2013.01.015. S0197-4580(13)00045-6 [pii].PubMedCentralPubMedGoogle Scholar
  52. 52.
    Namihira M, Nakashima K. Mechanisms of astrocytogenesis in the mammalian brain. Curr Opin Neurobiol. 2013;23(6):921–7. doi: 10.1016/j.conb.2013.06.002. S0959-4388(13)00121-9 [pii].PubMedGoogle Scholar
  53. 53.
    Benner EJ, Luciano D, Jo R, Abdi K, Paez-Gonzalez P, Sheng H, Warner DS, Liu C, Eroglu C, Kuo CT. Protective astrogenesis from the SVZ niche after injury is controlled by Notch modulator Thbs4. Nature. 2013;497(7449):369–73. doi: 10.1038/nature12069. nature12069 [pii].PubMedCentralPubMedGoogle Scholar
  54. 54.
    Mejia-Gervacio S, Murray K, Lledo PM. NKCC1 controls GABAergic signaling and neuroblast migration in the postnatal forebrain. Neural Dev. 2011;6:4. doi: 10.1186/1749-8104-6-4. 1749-8104-6-4 [pii].PubMedCentralPubMedGoogle Scholar
  55. 55.
    Rosengren S, Henson PM, Worthen GS. Migration-associated volume changes in neutrophils facilitate the migratory process in vitro. Am J Physiol. 1994;267(6 Pt 1):C1623–32.PubMedGoogle Scholar
  56. 56.
    Rotte A, Pasham V, Yang W, Eichenmuller M, Bhandaru M, Shumilina E, Lang F. Phosphoinositide 3-kinase-dependent regulation of Na+/H+ exchanger in dendritic cells. Pflugers Arch. 2010;460(6):1087–96. doi: 10.1007/s00424-010-0879-0.PubMedGoogle Scholar
  57. 57.
    Klein M, Seeger P, Schuricht B, Alper SL, Schwab A. Polarization of Na(+)/H(+) and Cl(−)/HCO (3)(−) exchangers in migrating renal epithelial cells. J Gen Physiol. 2000;115(5):599–608.PubMedCentralPubMedGoogle Scholar
  58. 58.
    Horesh D, Sapir T, Francis F, Wolf SG, Caspi M, Elbaum M, Chelly J, Reiner O. Doublecortin, a stabilizer of microtubules. Hum Mol Genet. 1999;8(9):1599–610.PubMedGoogle Scholar
  59. 59.
    Gleeson JG, Allen KM, Fox JW, Lamperti ED, Berkovic S, Scheffer I, Cooper EC, Dobyns WB, Minnerath SR, Ross ME, Walsh CA. doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein. Cell. 1998;92(1):63–72. doi: 10.1016/s0092-8674(00)80899-5.PubMedGoogle Scholar
  60. 60.
    Francis F, Koulakoff A, Boucher D, Chafey P, Schaar B, Vinet MC, Friocourt G, McDonnell N, Reiner O, Kahn A, McConnell SK, Berwald-Netter Y, Denoulet P, Chelly J. Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons. Neuron. 1999;23(2):247–56. doi:S0896-6273(00)80777-1 [pii].PubMedGoogle Scholar
  61. 61.
    Ocbina PJ, Dizon ML, Shin L, Szele FG. Doublecortin is necessary for the migration of adult subventricular zone cells from neurospheres. Mol Cell Neurosci. 2006;33(2):126–35. doi: 10.1016/j.mcn.2006.06.014. S1044-7431(06)00134-5 [pii].PubMedGoogle Scholar
  62. 62.
    Koizumi H, Higginbotham H, Poon T, Tanaka T, Brinkman BC, Gleeson JG. Doublecortin maintains bipolar shape and nuclear translocation during migration in the adult forebrain. Nat Neurosci. 2006;9(6):779–86. doi: 10.1038/nn1704. nn1704 [pii].PubMedGoogle Scholar
  63. 63.
    Kappeler C, Saillour Y, Baudoin JP, Tuy FP, Alvarez C, Houbron C, Gaspar P, Hamard G, Chelly J, Metin C, Francis F. Branching and nucleokinesis defects in migrating interneurons derived from doublecortin knockout mice. Hum Mol Genet. 2006;15(9):1387–400.PubMedGoogle Scholar
  64. 64.
    Sontheimer H. An unexpected role for ion channels in brain tumor metastasis. Exp Biol Med (Maywood). 2008;233(7):779–91. doi: 10.3181/0711-MR-308. 0711-MR-308 [pii].Google Scholar
  65. 65.
    Gamba G. Molecular physiology and pathophysiology of electroneutral cation-chloride cotransporters. Physiol Rev. 2005;85(2):423–93. doi: 10.1152/physrev.00011.2004. 85/2/423 [pii].PubMedGoogle Scholar
  66. 66.
    Lytle C, Forbush 3rd B. Regulatory phosphorylation of the secretory Na-K-Cl cotransporter: modulation by cytoplasmic Cl. Am J Physiol. 1996;270(2 Pt 1):C437–48.PubMedGoogle Scholar
  67. 67.
    Yamada J, Okabe A, Toyoda H, Kilb W, Luhmann HJ, Fukuda A. Cl-uptake promoting depolarizing GABA actions in immature rat neocortical neurones is mediated by NKCC1. J Physiol. 2004;557(Pt 3):829–41. doi: 10.1113/jphysiol.2004.062471. jphysiol.2004.062471 [pii].PubMedCentralPubMedGoogle Scholar
  68. 68.
    Russell JM. Sodium-potassium-chloride cotransport. Physiol Rev. 2000;80(1):211–76.PubMedGoogle Scholar
  69. 69.
    Strange K. Cellular volume homeostasis. Adv Physiol Educ. 2004;28(1–4):155–9. doi: 10.1152/advan.00034.2004. 28/4/155 [pii].PubMedGoogle Scholar
  70. 70.
    Garzon-Muvdi T, Schiapparelli P, Rhys C, Guerrero-Cazares H, Smith C, Kim DH, Kone L, Farber H, Lee DY, An SS, Levchenko A, Quinones-Hinojosa A. Regulation of brain tumor dispersal by NKCC1 through a novel role in focal adhesion regulation. PLoS Biol. 2012;10(5):e1001320. doi: 10.1371/journal.pbio.1001320. PBIOLOGY-D-11-02751 [pii].PubMedCentralPubMedGoogle Scholar
  71. 71.
    Ohshima T, Ward JM, Huh CG, Longenecker G, Veeranna PHC, Brady RO, Martin LJ, Kulkarni AB. Targeted disruption of the cyclin-dependent kinase 5 gene results in abnormal corticogenesis, neuronal pathology and perinatal death. Proc Natl Acad Sci U S A. 1996;93(20):11173–8.PubMedCentralPubMedGoogle Scholar
  72. 72.
    Gilmore EC, Ohshima T, Goffinet AM, Kulkarni AB, Herrup K. Cyclin-dependent kinase 5-deficient mice demonstrate novel developmental arrest in cerebral cortex. J Neurosci. 1998;18(16):6370–7.PubMedGoogle Scholar
  73. 73.
    Ohshima T, Hirasawa M, Tabata H, Mutoh T, Adachi T, Suzuki H, Saruta K, Iwasato T, Itohara S, Hashimoto M, Nakajima K, Ogawa M, Kulkarni AB, Mikoshiba K. Cdk5 is required for multipolar-to-bipolar transition during radial neuronal migration and proper dendrite development of pyramidal neurons in the cerebral cortex. Development. 2007;134(12):2273–82. doi: 10.1242/dev.02854. dev.02854 [pii].PubMedGoogle Scholar
  74. 74.
    Hirota Y, Ohshima T, Kaneko N, Ikeda M, Iwasato T, Kulkarni AB, Mikoshiba K, Okano H, Sawamoto K. Cyclin-dependent kinase 5 is required for control of neuroblast migration in the postnatal subventricular zone. J Neurosci. 2007;27(47):12829–38. doi:10.1523/JNEUROSCI. 1014-07.2007. 27/47/12829 [pii].Google Scholar
  75. 75.
    Bonfanti L, Olive S, Poulain DA, Theodosis DT. Mapping of the distribution of polysialylated neural cell adhesion molecule throughout the central nervous system of the adult rat: an immunohistochemical study. Neuroscience. 1992;49(2):419–36. doi:0306-4522(92)90107-D [pii].PubMedGoogle Scholar
  76. 76.
    Bonfanti L. PSA-NCAM in mammalian structural plasticity and neurogenesis. Prog Neurobiol. 2006;80(3):129–64. doi: 10.1016/j.pneurobio.2006.08.003.PubMedGoogle Scholar
  77. 77.
    Yang P, Yin X, Rutishauser U. Intercellular space is affected by the polysialic acid content of NCAM. J Cell Biol. 1992;116(6):1487–96.PubMedGoogle Scholar
  78. 78.
    Hu H, Tomasiewicz H, Magnuson T, Rutishauser U. The role of polysialic acid in migration of olfactory bulb interneuron precursors in the subventricular zone. Neuron. 1996;16(4):735–43. doi:S0896-6273(00)80094-X [pii].PubMedGoogle Scholar
  79. 79.
    Bonfanti L, Theodosis DT. Expression of polysialylated neural cell adhesion molecule by proliferating cells in the subependymal layer of the adult rat, in its rostral extension and in the olfactory bulb. Neuroscience. 1994;62(1):291–305. doi:0306-4522(94)90333-6 [pii].PubMedGoogle Scholar
  80. 80.
    Cremer H, Lange R, Christoph A, Plomann M, Vopper G, Roes J, Brown R, Baldwin S, Kraemer P, Scheff S, et al. Inactivation of the N-CAM gene in mice results in size reduction of the olfactory bulb and deficits in spatial learning. Nature. 1994;367(6462):455–9. doi: 10.1038/367455a0.PubMedGoogle Scholar
  81. 81.
    Chazal G, Durbec P, Jankovski A, Rougon G, Cremer H. Consequences of neural cell adhesion molecule deficiency on cell migration in the rostral migratory stream of the mouse. J Neurosci. 2000;20(4):1446–57.PubMedGoogle Scholar
  82. 82.
    Ono K, Tomasiewicz H, Magnuson T, Rutishauser U. N-CAM mutation inhibits tangential neuronal migration and is phenocopied by enzymatic removal of polysialic acid. Neuron. 1994;13(3):595–609. doi:0896-6273(94)90028-0 [pii].PubMedGoogle Scholar
  83. 83.
    Plow EF, Haas TA, Zhang L, Loftus J, Smith JW. Ligand binding to integrins. J Biol Chem. 2000;275(29):21785–8. doi: 10.1074/jbc.R000003200. R000003200 [pii].PubMedGoogle Scholar
  84. 84.
    Murase S, Horwitz AF. Deleted in colorectal carcinoma and differentially expressed integrins mediate the directional migration of neural precursors in the rostral migratory stream. J Neurosci. 2002;22(9):3568–79. doi:20026349. 22/9/3568 [pii].PubMedGoogle Scholar
  85. 85.
    Emsley JG, Hagg T. alpha6beta1 integrin directs migration of neuronal precursors in adult mouse forebrain. Exp Neurol. 2003;183(2):273–85. doi:S0014488603002097 [pii].PubMedGoogle Scholar
  86. 86.
    Mobley AK, McCarty JH. beta8 integrin is essential for neuroblast migration in the rostral migratory stream. Glia. 2011;59(11):1579–87. doi: 10.1002/glia.21199.PubMedGoogle Scholar
  87. 87.
    Tessier-Lavigne M. Wiring the brain: the logic and molecular mechanisms of axon guidance and regeneration. Harvey Lect. 2002;98:103–43.PubMedGoogle Scholar
  88. 88.
    Staquicini FI, Dias-Neto E, Li J, Snyder EY, Sidman RL, Pasqualini R, Arap W. Discovery of a functional protein complex of netrin-4, laminin gamma1 chain, and integrin alpha6beta1 in mouse neural stem cells. Proc Natl Acad Sci U S A. 2009;106(8):2903–8. doi: 10.1073/pnas.0813286106. 0813286106 [pii].PubMedCentralPubMedGoogle Scholar
  89. 89.
    Ingham PW, McMahon AP. Hedgehog signaling in animal development: paradigms and principles. Genes Dev. 2001;15(23):3059–87. doi: 10.1101/gad.938601.PubMedGoogle Scholar
  90. 90.
    Angot E, Loulier K, Nguyen-Ba-Charvet KT, Gadeau AP, Ruat M, Traiffort E. Chemoattractive activity of sonic hedgehog in the adult subventricular zone modulates the number of neural precursors reaching the olfactory bulb. Stem Cells. 2008;26(9):2311–20. doi:10.1634/stemcells. 2008-0297. 2008-0297 [pii].Google Scholar
  91. 91.
    Hor CH, Tang BL. Sonic hedgehog as a chemoattractant for adult NPCs. Cell Adh Migr. 2010;4(1):1–3. doi:9914 [pii].PubMedCentralPubMedGoogle Scholar
  92. 92.
    Ihrie RA, Shah JK, Harwell CC, Levine JH, Guinto CD, Lezameta M, Kriegstein AR, Alvarez-Buylla A. Persistent sonic hedgehog signaling in adult brain determines neural stem cell positional identity. Neuron. 2011;71(2):250–62. doi: 10.1016/j.neuron.2011.05.018. S0896-6273(11)00404-1 [pii].PubMedCentralPubMedGoogle Scholar
  93. 93.
    Nguyen-Ba-Charvet KT, Chedotal A. Role of Slit proteins in the vertebrate brain. J Physiol Paris. 2002;96(1–2):91–8. doi: 10.1016/s0928-4257(01)00084-5. Pii s0928-4257(01)00084-5.PubMedGoogle Scholar
  94. 94.
    Wong K, Park HT, Wu JY, Rao Y. Slit proteins: molecular guidance cues for cells ranging from neurons to leukocytes. Curr Opin Genet Dev. 2002;12(5):583–91. doi: 10.1016/s0959-437x(02)00343-x.PubMedGoogle Scholar
  95. 95.
    Chilton JK. Molecular mechanisms of axon guidance. Dev Biol. 2006;292(1):13–24. doi: 10.1016/j.ydbio.2005.12.048.PubMedGoogle Scholar
  96. 96.
    Nguyen-Ba-Charvet KT, Picard-Riera N, Tessier-Lavigne M, Baron-Van Evercooren A, Sotelo C, Chedotal A. Multiple roles for slits in the control of cell migration in the rostral migratory stream. J Neurosci. 2004;24(6):1497–506. doi:10.1523/jneurosci. 4729-03.2004.Google Scholar
  97. 97.
    Kitabgi P, Melik-Parsadaniantz S, Rostene W (2006) Chemokines: a new peptide family of neuromodulators. Handbook of Biologically Active Peptides. p. 559–565. doi:10.1016/B978-012369442-3/50083-0.Google Scholar
  98. 98.
    Schonemeier B, Kolodziej A, Schulz S, Jacobs S, Hoellt V, Stumm R. Regional and cellular localization of the CXCl12/SDF-1 chemokine receptor CXCR7 in the developing and adult rat brain. J Comp Neurol. 2008;510(2):207–20. doi: 10.1002/cne.21780.PubMedGoogle Scholar
  99. 99.
    Odemis V, Boosmann K, Heinen A, Kury P, Engele J. CXCR7 is an active component of SDF-1 signalling in astrocytes and Schwann cells. J Cell Sci. 2010;123(Pt 7):1081–8. doi: 10.1242/jcs.062810.PubMedGoogle Scholar
  100. 100.
    Tiveron MC, Boutin C, Daou P, Moepps B, Cremer H. Expression and function of CXCR7 in the mouse forebrain. J Neuroimmunol. 2010;224(1–2):72–9.PubMedGoogle Scholar
  101. 101.
    Kojima T, Hirota Y, Ema M, Takahashi S, Miyoshi I, Okano H, Sawamoto K. Subventricular zone-derived neural progenitor cells migrate along a blood vessel scaffold toward the post-stroke striatum. Stem Cells. 2010;28(3):545–54. doi: 10.1002/stem.306.PubMedGoogle Scholar
  102. 102.
    Arvidsson A, Collin T, Kirik D, Kokaia Z, Lindvall O. Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med. 2002;8(9):963–70. doi: 10.1038/nm747. nm747 [pii].PubMedGoogle Scholar
  103. 103.
    Liu BF, Gao EJ, Zeng XZ, Ji M, Cai Q, Lu Q, Yang H, Xu QY. Proliferation of neural precursors in the subventricular zone after chemical lesions of the nigrostriatal pathway in rat brain. Brain Res. 2006;1106(1):30–9. doi: 10.1016/j.brainres.2006.05.111. S0006-8993(06)01534-4 [pii].PubMedGoogle Scholar
  104. 104.
    Nait-Oumesmar B, Picard-Riera N, Kerninon C, Decker L, Seilhean D, Hoglinger GU, Hirsch EC, Reynolds R, Baron-Van Evercooren A. Activation of the subventricular zone in multiple sclerosis: evidence for early glial progenitors. Proc Natl Acad Sci U S A. 2007;104(11):4694–9.PubMedCentralPubMedGoogle Scholar
  105. 105.
    Otero L, Zurita M, Bonilla C, Rico MA, Aguayo C, Rodriguez A, Vaquero J. Endogenous neurogenesis after intracerebral hemorrhage. Histol Histopathol. 2012;27(3):303–15.PubMedGoogle Scholar
  106. 106.
    Del Carmen Gomez-Roldan M, Perez-Martin M, Capilla-Gonzalez V, Cifuentes M, Perez J, Garcia-Verdugo JM, Fernandez-Llebrez P. Neuroblast proliferation on the surface of the adult rat striatal wall after focal ependymal loss by intracerebroventricular injection of neuraminidase. J Comp Neurol. 2008;507(4):1571–87. doi: 10.1002/cne.21618.PubMedGoogle Scholar
  107. 107.
    Menn B, Garcia-Verdugo JM, Yaschine C, Gonzalez-Perez O, Rowitch D, Alvarez-Buylla A. Origin of oligodendrocytes in the subventricular zone of the adult brain. J Neurosci. 2006;26(30):7907–18. doi:10.1523/JNEUROSCI. 1299-06.2006. 26/30/7907 [pii].Google Scholar
  108. 108.
    Picard-Riera N, Decker L, Delarasse C, Goude K, Nait-Oumesmar B, Liblau R, Pham-Dinh D, Evercooren AB. Experimental autoimmune encephalomyelitis mobilizes neural progenitors from the subventricular zone to undergo oligodendrogenesis in adult mice. Proc Natl Acad Sci U S A. 2002;99(20):13211–6. doi: 10.1073/pnas.192314199. 192314199 [pii].PubMedCentralPubMedGoogle Scholar
  109. 109.
    Gonzalez-Perez O, Romero-Rodriguez R, Soriano-Navarro M, Garcia-Verdugo JM, Alvarez-Buylla A. Epidermal growth factor induces the progeny of subventricular zone type B cells to migrate and differentiate into oligodendrocytes. Stem Cells. 2009;27(8):2032–43. doi: 10.1002/stem.119.PubMedCentralPubMedGoogle Scholar
  110. 110.
    Kaneko N, Sawamoto K. Neuronal migration in the adult brain. Nihon Shinkei Seishin Yakurigaku Zasshi. 2007;27(5–6):215–8.PubMedGoogle Scholar
  111. 111.
    Gonzalez-Perez O, Gutierrez-Fernandez F, Lopez-Virgen V, Collas-Aguilar J, Quinones-Hinojosa A, Garcia-Verdugo JM. Immunological regulation of neurogenic niches in the adult brain. Neuroscience. 2012;226:270–81. doi: 10.1016/j.neuroscience.2012.08.053. S0306-4522(12)00888-3 [pii].PubMedCentralPubMedGoogle Scholar
  112. 112.
    Logan TT, Villapol S, Symes AJ. TGF-beta superfamily gene expression and induction of the Runx1 transcription factor in adult neurogenic regions after brain injury. PLoS One. 2013;8(3):e59250. doi: 10.1371/journal.pone.0059250. PONE-D-12-27158 [pii].PubMedCentralPubMedGoogle Scholar
  113. 113.
    Yan YP, Sailor KA, Vemuganti R, Dempsey RJ. Insulin-like growth factor-1 is an endogenous mediator of focal ischemia-induced neural progenitor proliferation. Eur J Neurosci. 2006;24(1):45–54. doi: 10.1111/j.1460-9568.2006.04872.x. EJN4872 [pii].PubMedGoogle Scholar
  114. 114.
    Kang SS, Keasey MP, Arnold SA, Reid R, Geralds J, Hagg T. Endogenous CNTF mediates stroke-induced adult CNS neurogenesis in mice. Neurobiol Dis. 2012;49C:68–78. doi: 10.1016/j.nbd.2012.08.020. S0969-9961(12)00307-5 [pii].Google Scholar
  115. 115.
    Pluchino S, Muzio L, Imitola J, Deleidi M, Alfaro-Cervello C, Salani G, Porcheri C, Brambilla E, Cavasinni F, Bergamaschi A, Garcia-Verdugo JM, Comi G, Khoury SJ, Martino G. Persistent inflammation alters the function of the endogenous brain stem cell compartment. Brain. 2008;131(Pt 10):2564–78. doi: 10.1093/brain/awn198. awn198 [pii].PubMedCentralPubMedGoogle Scholar
  116. 116.
    Imitola J, Raddassi K, Park KI, Mueller FJ, Nieto M, Teng YD, Frenkel D, Li J, Sidman RL, Walsh CA, Snyder EY, Khoury SJ. Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor 4 pathway. Proc Natl Acad Sci U S A. 2004;101(52):18117–22. doi: 10.1073/pnas.0408258102. 0408258102 [pii].PubMedCentralPubMedGoogle Scholar
  117. 117.
    Tran PB, Ren D, Veldhouse TJ, Miller RJ. Chemokine receptors are expressed widely by embryonic and adult neural progenitor cells. J Neurosci Res. 2004;76(1):20–34. doi: 10.1002/jnr.20001.PubMedGoogle Scholar
  118. 118.
    Jaerve A, Muller HW. Chemokines in CNS injury and repair. Cell Tissue Res. 2012;349(1):229–48. doi: 10.1007/s00441-012-1427-3.PubMedGoogle Scholar
  119. 119.
    Turbic A, Leong SY, Turnley AM. Chemokines and inflammatory mediators interact to regulate adult murine neural precursor cell proliferation, survival and differentiation. PLoS One. 2011;6(9):e25406. doi: 10.1371/journal.pone.0025406. PONE-D-11-06373 [pii].PubMedCentralPubMedGoogle Scholar
  120. 120.
    Belmadani A, Tran PB, Ren D, Miller RJ. Chemokines regulate the migration of neural progenitors to sites of neuroinflammation. J Neurosci. 2006;26(12):3182–91. doi:10.1523/JNEUROSCI. 0156-06.2006. 26/12/3182 [pii].Google Scholar
  121. 121.
    Gordon RJ, Mehrabi NF, Maucksch C, Connor B. Chemokines influence the migration and fate of neural precursor cells from the young adult and middle-aged rat subventricular zone. Experimental neurology. 2012;233(1):587–94. doi: 10.1016/j.expneurol.2011.11.029. S0014-4886(11)00433-X [pii].PubMedGoogle Scholar
  122. 122.
    Widera D, Holtkamp W, Entschladen F, Niggemann B, Zanker K, Kaltschmidt B, Kaltschmidt C. MCP-1 induces migration of adult neural stem cells. Eur J Cell Biol. 2004;83(8):381–7. doi: 10.1078/0171-9335-00403. S0171-9335(04)70406-9 [pii].PubMedGoogle Scholar
  123. 123.
    Gordon RJ, McGregor AL, Connor B. Chemokines direct neural progenitor cell migration following striatal cell loss. Mol Cell Neurosci. 2009;41(2):219–32. doi: 10.1016/j.mcn.2009.03.001. S1044-7431(09)00061-X [pii].PubMedGoogle Scholar
  124. 124.
    Liu XS, Zhang ZG, Zhang RL, Gregg SR, Wang L, Yier T, Chopp M. Chemokine ligand 2 (CCL2) induces migration and differentiation of subventricular zone cells after stroke. J Neurosci Res. 2007;85(10):2120–5. doi: 10.1002/jnr.21359.PubMedGoogle Scholar
  125. 125.
    Yan YP, Sailor KA, Lang BT, Park SW, Vemuganti R, Dempsey RJ. Monocyte chemoattractant protein-1 plays a critical role in neuroblast migration after focal cerebral ischemia. J Cereb Blood Flow Metab. 2007;27(6):1213–24. doi: 10.1038/sj.jcbfm.9600432. 9600432 [pii].PubMedGoogle Scholar
  126. 126.
    Saha B, Peron S, Murray K, Jaber M, Gaillard A. Cortical lesion stimulates adult subventricular zone neural progenitor cell proliferation and migration to the site of injury. Stem Cell Res. 2013;11(3):965–77. doi: 10.1016/j.scr.2013.06.006. S1873-5061(13)00079-2 [pii].PubMedGoogle Scholar
  127. 127.
    Thored P, Arvidsson A, Cacci E, Ahlenius H, Kallur T, Darsalia V, Ekdahl CT, Kokaia Z, Lindvall O. Persistent production of neurons from adult brain stem cells during recovery after stroke. Stem Cells. 2006;24(3):739–47. doi:10.1634/stemcells. 2005-0281. 2005–0281 [pii].Google Scholar
  128. 128.
    Robin AM, Zhang ZG, Wang L, Zhang RL, Katakowski M, Zhang L, Wang Y, Zhang C, Chopp M. Stromal cell-derived factor 1alpha mediates neural progenitor cell motility after focal cerebral ischemia. J Cereb Blood Flow Metab. 2006;26(1):125–34. doi: 10.1038/sj.jcbfm.9600172. 9600172 [pii].PubMedGoogle Scholar
  129. 129.
    Itoh T, Satou T, Ishida H, Nishida S, Tsubaki M, Hashimoto S, Ito H. The relationship between SDF-1alpha/CXCR4 and neural stem cells appearing in damaged area after traumatic brain injury in rats. Neurol Res. 2009;31(1):90–102. doi: 10.1179/174313208X332995.PubMedGoogle Scholar
  130. 130.
    Aguirre A, Gallo V. Reduced EGFR signaling in progenitor cells of the adult subventricular zone attenuates oligodendrogenesis after demyelination. Neuron Glia Biol. 2007;3(3):209–20. doi: 10.1017/S1740925X08000082. S1740925X08000082 [pii].PubMedCentralPubMedGoogle Scholar
  131. 131.
    Decker L, Picard-Riera N, Lachapelle F, Baron-Van Evercooren A. Growth factor treatment promotes mobilization of young but not aged adult subventricular zone precursors in response to demyelination. J Neurosci Res. 2002;69(6):763–71. doi: 10.1002/jnr.10411.PubMedGoogle Scholar
  132. 132.
    Lachapelle F, Avellana-Adalid V, Nait-Oumesmar B, Baron-Van Evercooren A. Fibroblast growth factor-2 (FGF-2) and platelet-derived growth factor AB (PDGF AB) promote adult SVZ-derived oligodendrogenesis in vivo. Mol Cell Neurosci. 2002;20(3):390–403. doi:S1044743102911243 [pii].PubMedGoogle Scholar
  133. 133.
    Wang Y, Jin K, Mao XO, Xie L, Banwait S, Marti HH, Greenberg DA. VEGF-overexpressing transgenic mice show enhanced post-ischemic neurogenesis and neuromigration. J Neurosci Res. 2007;85(4):740–7. doi: 10.1002/jnr.21169.PubMedGoogle Scholar
  134. 134.
    Bao X, Wei J, Feng M, Lu S, Li G, Dou W, Ma W, Ma S, An Y, Qin C, Zhao RC, Wang R. Transplantation of human bone marrow-derived mesenchymal stem cells promotes behavioral recovery and endogenous neurogenesis after cerebral ischemia in rats. Brain Res. 2011;1367:103–13. doi: 10.1016/j.brainres.2010.10.063. S0006-8993(10)02332-2 [pii].PubMedGoogle Scholar
  135. 135.
    Harms KM, Li L, Cunningham LA. Murine neural stem/progenitor cells protect neurons against ischemia by HIF-1alpha-regulated VEGF signaling. PLoS One. 2010;5(3):e9767. doi: 10.1371/journal.pone.0009767.PubMedCentralPubMedGoogle Scholar
  136. 136.
    Barkho BZ, Munoz AE, Li X, Li L, Cunningham LA, Zhao X. Endogenous matrix metalloproteinase (MMP)-3 and MMP-9 promote the differentiation and migration of adult neural progenitor cells in response to chemokines. Stem Cells. 2008;26(12):3139–49. doi:10.1634/stemcells. 2008-0519. 2008-0519 [pii].Google Scholar
  137. 137.
    Courtes S, Vernerey J, Pujadas L, Magalon K, Cremer H, Soriano E, Durbec P, Cayre M. Reelin controls progenitor cell migration in the healthy and pathological adult mouse brain. PLoS One. 2011;6(5):e20430. doi: 10.1371/journal.pone.0020430. PONE-D-11-03174 [pii].PubMedCentralPubMedGoogle Scholar
  138. 138.
    Aboody KS, Najbauer J, Danks MK. Stem and progenitor cell-mediated tumor selective gene therapy. Gene Ther. 2008;15(10):739–52. doi: 10.1038/gt.2008.41.PubMedGoogle Scholar
  139. 139.
    McGirt MJ, Chaichana KL, Gathinji M, Attenello FJ, Than K, Olivi A, Weingart JD, Brem H, Quinones-Hinojosa AR. Independent association of extent of resection with survival in patients with malignant brain astrocytoma. J Neurosurg. 2009;110(1):156–62. doi: 10.3171/2008.4.17536.PubMedGoogle Scholar
  140. 140.
    Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–96. doi: 10.1056/NEJMoa043330.PubMedGoogle Scholar
  141. 141.
    Aboody KS, Brown A, Rainov NG, Bower KA, Liu S, Yang W, Small JE, Herrlinger U, Ourednik V, Black PM, Breakefield XO, Snyder EY. Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas. Proc Natl Acad Sci U S A. 2000;97(23):12846–51. doi: 10.1073/pnas.97.23.12846.PubMedCentralPubMedGoogle Scholar
  142. 142.
    Zhao D, Najbauer J, Garcia E, Metz MZ, Gutova M, Glackin CA, Kim SU, Aboody KS. Neural stem cell tropism to glioma: critical role of tumor hypoxia. Mol Cancer Res. 2008;6(12):1819–29. doi: 10.1158/1541-7786.MCR-08-0146.PubMedGoogle Scholar
  143. 143.
    Ziu M, Schmidt NO, Cargioli TG, Aboody KS, Black PM, Carroll RS. Glioma-produced extracellular matrix influences brain tumor tropism of human neural stem cells. J Neurooncol. 2006;79(2):125–33. doi: 10.1007/s11060-006-9121-5.PubMedGoogle Scholar
  144. 144.
    Kendall SE, Najbauer J, Johnston HF, Metz MZ, Li S, Bowers M, Garcia E, Kim SU, Barish ME, Aboody KS, Glackin CA. Neural stem cell targeting of glioma is dependent on phosphoinositide 3-kinase signaling. Stem Cells. 2008;26(6):1575–86. doi:10.1634/stemcells. 2007-0887.Google Scholar
  145. 145.
    Frank RT, Najbauer J, Aboody KS. Concise review: stem cells as an emerging platform for antibody therapy of cancer. Stem Cells. 2010;28(11):2084–7. doi: 10.1002/stem.513.PubMedCentralPubMedGoogle Scholar
  146. 146.
    Aboody KS, Najbauer J, Metz MZ, D’Apuzzo M, Gutova M, Annala AJ, Synold TW, Couture LA, Blanchard S, Moats RA, Garcia E, Aramburo S, Valenzuela VV, Frank RT, Barish ME, Brown CE, Kim SU, Badie B, Portnow J. Neural stem cell-mediated enzyme/prodrug therapy for glioma: preclinical studies. Sci Transl Med. 2013;5(184):184ra159. doi: 10.1126/scitranslmed.3005365.Google Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Vivian Capilla-Gonzalez
    • 1
    • 2
  • Emily Lavell
    • 2
  • Alfredo Quiñones-Hinojosa
    • 2
  • Hugo Guerrero-Cazares
    • 3
    Email author
  1. 1.Stem Cells DepartmentAndalusian Molecular Biology and Regenerative Medicine CentreSevilleSpain
  2. 2.Department of Neurosurgery and OncologyJohns Hopkins University School of MedicineBaltimoreUSA
  3. 3.Department of NeurosurgeryJohns Hopkins UniversityBaltimoreUSA

Personalised recommendations