Neuronal stem cells in the central nervous system and in human diseases

Abstract

The process of cortical expansion in the central nervous system is a key step of mammalian brain development to ensure its physiological function. Radial glial (RG) cells are a glial cell type contributing to this progress as intermediate neural progenitor cells responsible for an increase in the number of cortical neurons. In this review, we discuss the current understanding of RG cells during neurogenesis and provide further information on the mechanisms of neurodevelopmental diseases and stem cell-related brain tumorigenesis. Knowledge of neuronal stem cell and relative diseases will bridge benchmark research through translational studies to clinical therapeutic treatments of these diseases.

Keywords

radial glial cell / neuronal stem cell / tumorigenesis / glioma

References

[1] Alkuraya, F.S., Cai, X., Emery, C., Mochida, G.H., Al-Dosari, M.S., Felie, J.M., Hill, R.S., Barry, B.J., Partlow, J.N., Gascon, G.G., . (2011). Human mutations in NDE1 cause extreme microcephaly with lissencephaly [corrected]. Am J Hum Genet 88, 536-547 .10.1016/j.ajhg.2011.04.003
[2] Alvarez-Buylla, A., and Garcia-Verdugo, J.M. (2002). Neurogenesis in adult subventricular zone. J Neurosci 22, 629-634 .
[3] Alvarez-Buylla, A., Kirn, J.R., and Nottebohm, F. (1990). Birth of projection neurons in adult avian brain may be related to perceptual or motor learning. Science 249, 1444-1446 .10.1126/science.1698312
[4] Anderson, S.A., Eisenstat, D.D., Shi, L., and Rubenstein, J.L. (1997). Interneuron migration from basal forebrain to neocortex: dependence on Dlx genes. Science 278, 474-476 .10.1126/science.278.5337.474
[5] Assanah, M., Lochhead, R., Ogden, A., Bruce, J., Goldman, J., and Canoll, P. (2006). Glial progenitors in adult white matter are driven to form malignant gliomas by platelet-derived growth factor-expressing retroviruses. J Neurosci 26, 6781-6790 .10.1523/JNEUROSCI.0514-06.2006
[6] Bachoo, R.M., Maher, E.A., Ligon, K.L., Sharpless, N.E., Chan, S.S., You, M.J., Tang, Y., DeFrances, J., Stover, E., Weissleder, R., . (2002). Epidermal growth factor receptor and Ink4a/Arf: convergent mechanisms governing terminal differentiation and transformation along the neural stem cell to astrocyte axis. Cancer Cell 1, 269-277 .10.1016/S1535-6108(02)00046-6
[7] Bao, S., Wu, Q., McLendon, R.E., Hao, Y., Shi, Q., Hjelmeland, A.B., Dewhirst, M.W., Bigner, D.D., and Rich, J.N. (2006a). Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444, 756-760 .10.1038/nature05236
[8] Bao, S., Wu, Q., Sathornsumetee, S., Hao, Y., Li, Z., Hjelmeland, A.B., Shi, Q., McLendon, R.E., Bigner, D.D., and Rich, J.N. (2006b). Stem cell-like glioma cells promote tumor angiogenesis through vascular endothelial growth factor. Cancer Res 66, 7843-7848 .10.1158/0008-5472.CAN-06-1010
[9] Barrera, J.A., Kao, L.R., Hammer, R.E., Seemann, J., Fuchs, J.L., and Megraw, T.L. (2010). CDK5RAP2 regulates centriole engagement and cohesion in mice. Dev Cell 18, 913-926 .10.1016/j.devcel.2010.05.017
[10] Bauman, M.L. (1987). Neuroembryology—clinical aspects. Semin Perinatol 11, 74-84 .
[11] Ben-Porath, I., Thomson, M.W., Carey, V.J., Ge, R., Bell, G.W., Regev, A., and Weinberg, R.A. (2008). An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet 40, 499-507 .10.1038/ng.127
[12] Benedito, R., and Duarte, A. (2005). Expression of Dll4 during mouse embryogenesis suggests multiple developmental roles. Gene Expr Patterns 5, 750-755 .10.1016/j.modgep.2005.04.004
[13] Birnbaum, T., Roider, J., Schankin, C.J., Padovan, C.S., Schichor, C., Goldbrunner, R., and Straube, A. (2007). Malignant gliomas actively recruit bone marrow stromal cells by secreting angiogenic cytokines. J Neurooncol 83, 241-247 .10.1007/s11060-007-9332-4
[14] Bond, J., Roberts, E., Springell, K., Lizarraga, S.B., Scott, S., Higgins, J., Hampshire, D.J., Morrison, E.E., Leal, G.F., Silva, E.O., . (2005). A centrosomal mechanism involving CDK5RAP2 and CENPJ controls brain size. Nat Genet 37, 353-355 .10.1038/ng1539
[15] Buchman, J.J., Tseng, H.C., Zhou, Y., Frank, C.L., Xie, Z., and Tsai, L.H. (2010). Cdk5rap2 interacts with pericentrin to maintain the neural progenitor pool in the developing neocortex. Neuron 66, 386-402 .10.1016/j.neuron.2010.03.036
[16] Calabrese, C., Poppleton, H., Kocak, M., Hogg, T.L., Fuller, C., Hamner, B., Oh, E.Y., Gaber, M.W., Finklestein, D., Allen, M., . (2007). A perivascular niche for brain tumor stem cells. Cancer Cell 11, 69-82 .10.1016/j.ccr.2006.11.020
[17] Chen, R., Nishimura, M.C., Bumbaca, S.M., Kharbanda, S., Forrest, W.F., Kasman, I.M., Greve, J.M., Soriano, R.H., Gilmour, L.L., Rivers, C.S., . (2010). A hierarchy of self-renewing tumor-initiating cell types in glioblastoma. Cancer Cell 17, 362-375 .10.1016/j.ccr.2009.12.049
[18] Cheng, L., Wu, Q., Huang, Z., Guryanova, O.A., Huang, Q., Shou, W., Rich, J.N., and Bao, S. (2011). L1CAM regulates DNA damage checkpoint response of glioblastoma stem cells through NBS1. EMBO J 30, 800-813 .10.1038/emboj.2011.10
[19] Choi, Y.K., Liu, P., Sze, S.K., Dai, C., and Qi, R.Z. (2010). CDK5RAP2 stimulates microtubule nucleation by the gamma- tubulin ring complex. J Cell Biol 191, 1089-1095 .10.1083/jcb.201007030
[20] Cooper, J.A. (2008). A mechanism for inside-out lamination in the neocortex. Trends Neurosci 31, 113-119 .10.1016/j.tins.2007.12.003
[21] Corbin, J.G., Gaiano, N., Juliano, S.L., Poluch, S., Stancik, E., and Haydar, T.F. (2008). Regulation of neural progenitor cell development in the nervous system. J Neurochem 106, 2272-2287 .10.1111/j.1471-4159.2008.05522.x
[22] Dai, C., Celestino, J.C., Okada, Y., Louis, D.N., Fuller, G.N., and Holland, E.C. (2001). PDGF autocrine stimulation dedifferentiates cultured astrocytes and induces oligodendrogliomas and oligoastrocytomas from neural progenitors and astrocytes in vivo. Genes Dev 15, 1913-1925 .10.1101/gad.903001
[23] Dobyns, W.B. (1987). Developmental aspects of lissencephaly and the lissencephaly syndromes. Birth Defects Orig Artic Ser 23, 225-241 .
[24] Elias, L.A.B., Wang, D.D., and Kriegstein, A.R. (2007). Gap junction adhesion is necessary for radial migration in the neocortex. Nature 448, 901-907 .10.1038/nature06063
[25] Eyler, C.E., Foo, W.C., LaFiura, K.M., McLendon, R.E., Hjelmeland, A.B., and Rich, J.N. (2008). Brain cancer stem cells display preferential sensitivity to Akt inhibition. Stem Cells 26, 3027-3036 .10.1634/stemcells.2007-1073
[26] Facchino, S., Abdouh, M., Chatoo, W., and Bernier, G. (2010). BMI1 confers radioresistance to normal and cancerous neural stem cells through recruitment of the DNA damage response machinery. J Neurosci 30, 10096-10111 .10.1523/JNEUROSCI.1634-10.2010
[27] Fan, X., Khaki, L., Zhu, T.S., Soules, M.E., Talsma, C.E., Gul, N., Koh, C., Zhang, J., Li, Y.M., Maciaczyk, J., . (2010). NOTCH pathway blockade depletes CD133-positive glioblastoma cells and inhibits growth of tumor neurospheres and xenografts. Stem Cells 28, 5-16 .
[28] Ferrara, N. (2004). Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 25, 581-611 .10.1210/er.2003-0027
[29] Gal, J.S., Morozov, Y.M., Ayoub, A.E., Chatterjee, M., Rakic, P., and Haydar, T.F. (2006). Molecular and morphological heterogeneity of neural precursors in the mouse neocortical proliferative zones. J Neurosci 26, 1045-1056 .10.1523/JNEUROSCI.4499-05.2006
[30] Ghannad, M. (2011). The essential role of NDE1 in extreme microcephaly. Clin Genet 80, 241-242 .10.1111/j.1399-0004.2011.01753.x
[31] Glass, R., Synowitz, M., Kronenberg, G., Walzlein, J.H., Markovic, D.S., Wang, L.P., Gast, D., Kiwit, J., Kempermann, G., and Kettenmann, H. (2005). Glioblastoma-induced attraction of endogenous neural precursor cells is associated with improved survival. J Neurosci 25, 2637-2646 .10.1523/JNEUROSCI.5118-04.2005
[32] Gordon, W.R., Arnett, K.L., and Blacklow, S.C. (2008). The molecular logic of Notch signaling—a structural and biochemical perspective. J Cell Sci 121, 3109-3119 .10.1242/jcs.035683
[33] Gray, G.E., and Sanes, J.R. (1992). Lineage of radial glia in the chicken optic tectum. Development 114, 271-283 .
[34] Griffero, F., Daga, A., Marubbi, D., Capra, M.C., Melotti, A., Pattarozzi, A., Gatti, M., Bajetto, A., Porcile, C., Barbieri, F., . (2009). Different response of human glioma tumor-initiating cells to epidermal growth factor receptor kinase inhibitors. J Biol Chem 284, 7138-7148 .10.1074/jbc.M807111200
[35] Halliday, A.L., and Cepko, C.L. (1992). Generation and migration of cells in the developing striatum. Neuron 9, 15-26 .10.1016/0896-6273(92)90216-Z
[36] Haubensak, W., Attardo, A., Denk, W., and Huttner, W.B. (2004). Neurons arise in the basal neuroepithelium of the early mammalian telencephalon: a major site of neurogenesis. Proc Natl Acad Sci U S A 101, 3196-3201 .10.1073/pnas.0308600100
[37] Hegi, M.E., Diserens, A.C., Gorlia, T., Hamou, M.F., de Tribolet, N., Weller, M., Kros, J.M., Hainfellner, J.A., Mason, W., Mariani, L., . (2005). MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352, 997-1003 .10.1056/NEJMoa043331
[38] Higgins, J., Midgley, C., Bergh, A.M., Bell, S.M., Askham, J.M., Roberts, E., Binns, R.K., Sharif, S.M., Bennett, C., Glover, D.M., . (2010). Human ASPM participates in spindle organisation, spindle orientation and cytokinesis. BMC Cell Biol 11, 85.10.1186/1471-2121-11-85
[39] Holmberg, J., He, X., Peredo, I., Orrego, A., Hesselager, G., Ericsson, C., Hovatta, O., Oba-Shinjo, S.M., Marie, S.K., Nistér, M., . (2011). Activation of neural and pluripotent stem cell signatures correlates with increased malignancy in human glioma. PLoS One 6, e18454.10.1371/journal.pone.0018454
[40] Hopewell, J.W. (1975). The subependymal plate and the genesis of gliomas. J Pathol 117, 101-103 .10.1002/path.1711170208
[41] Ignatova, T.N., Kukekov, V.G., Laywell, E.D., Suslov, O.N., Vrionis, F.D., and Steindler, D.A. (2002). Human cortical glial tumors contain neural stem-like cells expressing astroglial and neuronal markers in vitro. Glia 39, 193-206 .10.1002/glia.10094
[42] Jackson, A.P., Eastwood, H., Bell, S.M., Adu, J., Toomes, C., Carr, I.M., Roberts, E., Hampshire, D.J., Crow, Y.J., Mighell, A.J., . (2002). Identification of microcephalin, a protein implicated in determining the size of the human brain. Am J Hum Genet 71, 136-142 .10.1086/341283
[43] Jackson, A.P., McHale, D.P., Campbell, D.A., Jafri, H., Rashid, Y., Mannan, J., Karbani, G., Corry, P., Levene, M.I., Mueller, R.F., . (1998). Primary autosomal recessive microcephaly (MCPH1) maps to chromosome 8p22-pter. Am J Hum Genet 63, 541-546 .10.1086/301966
[44] Kaindl, A.M., Passemard, S., Kumar, P., Kraemer, N., Issa, L., Zwirner, A., Gerard, B., Verloes, A., Mani, S., and Gressens, P. (2010). Many roads lead to primary autosomal recessive microcephaly. Prog Neurobiol 90, 363-383 .10.1016/j.pneurobio.2009.11.002
[45] Kornblum, H.I., Hussain, R., Wiesen, J., Miettinen, P., Zurcher, S.D., Chow, K., Derynck, R., and Werb, Z. (1998). Abnormal astrocyte development and neuronal death in mice lacking the epidermal growth factor receptor. J Neurosci Res 53, 697-717 .10.1002/(SICI)1097-4547(19980915)53:6<697::AID-JNR8>3.0.CO;2-0
[46] Kouprina, N., Pavlicek, A., Collins, N.K., Nakano, M., Noskov, V.N., Ohzeki, J., Mochida, G.H., Risinger, J.I., Goldsmith, P., Gunsior, M., . (2005). The microcephaly ASPM gene is expressed in proliferating tissues and encodes for a mitotic spindle protein. Hum Mol Genet 14, 2155-2165 .10.1093/hmg/ddi220
[47] Kovall, R.A. (2008). More complicated than it looks: assembly of Notch pathway transcription complexes. Oncogene 27, 5099-5109 .10.1038/onc.2008.223
[48] Kriegstein, A., Noctor, S., and Martínez-Cerde?o, V. (2006). Patterns of neural stem and progenitor cell division may underlie evolutionary cortical expansion. Nat Rev Neurosci 7, 883-890 .10.1038/nrn2008
[49] Kriegstein, A.R., and G?tz, M. (2003). Radial glia diversity: a matter of cell fate. Glia 43, 37-43 .10.1002/glia.10250
[50] Kumar, A., Girimaji, S.C., Duvvari, M.R., and Blanton, S.H. (2009). Mutations in STIL, encoding a pericentriolar and centrosomal protein, cause primary microcephaly. Am J Hum Genet 84, 286-290 .10.1016/j.ajhg.2009.01.017
[51] Lendahl, U., Zimmerman, L.B., and McKay, R.D. (1990). CNS stem cells express a new class of intermediate filament protein. Cell 60, 585-595 .10.1016/0092-8674(90)90662-X
[52] Levitt, P., and Rakic, P. (1980). Immunoperoxidase localization of glial fibrillary acidic protein in radial glial cells and astrocytes of the developing rhesus monkey brain. J Comp Neurol 193, 815-840 .10.1002/cne.901930316
[53] Lin, J., Zhang, X.M., Yang, J.C., Ye, Y.B., and Luo, S.Q. (2010). g-secretase inhibitor-I enhances radiosensitivity of glioblastoma cell lines by depleting CD133+ tumor cells. Arch Med Res 41, 519-529 .10.1016/j.arcmed.2010.10.006
[54] Liu, G., Yuan, X., Zeng, Z., Tunici, P., Ng, H., Abdulkadir, I.R., Lu, L., Irvin, D., Black, K.L., and Yu, J.S. (2006). Analysis of gene expression and chemoresistance of CD133+ cancer stem cells in glioblastoma. Mol Cancer 5, 67.10.1186/1476-4598-5-67
[55] LoTurco, J.J., Blanton, M.G., and Kriegstein, A.R. (1991). Initial expression and endogenous activation of NMDA channels in early neocortical development. J Neurosci 11, 792-799 .
[56] Luskin, M.B., Parnavelas, J.G., and Barfield, J.A. (1993). Neurons, astrocytes, and oligodendrocytes of the rat cerebral cortex originate from separate progenitor cells: an ultrastructural analysis of clonally related cells. J Neurosci 13, 1730-1750 .
[57] Maher, E.A., Furnari, F.B., Bachoo, R.M., Rowitch, D.H., Louis, D.N., Cavenee, W.K., and DePinho, R.A. (2001). Malignant glioma: genetics and biology of a grave matter. Genes Dev 15, 1311-1333 .10.1101/gad.891601
[58] Malatesta, P., Hartfuss, E., and G?tz, M. (2000). Isolation of radial glial cells by fluorescent-activated cell sorting reveals a neuronal lineage. Development 127, 5253-5263 .
[59] Mapara, K.Y., Stevenson, C.B., Thompson, R.C., and Ehtesham, M. (2007). Stem cells as vehicles for the treatment of brain cancer. [ix.] Neurosurg Clin N Am 18, 71-80 , ix.10.1016/j.nec.2006.10.001
[60] Martínez-Cerde?o, V., Noctor, S.C., and Kriegstein, A.R. (2006). The role of intermediate progenitor cells in the evolutionary expansion of the cerebral cortex. Cereb Cortex 16, i152-i161 .10.1093/cercor/bhk017
[61] Masui, K., Suzuki, S.O., Torisu, R., Goldman, J.E., Canoll, P., and Iwaki, T. (2010). Glial progenitors in the brainstem give rise to malignant gliomas by platelet-derived growth factor stimulation. Glia 58, 1050-1065 .10.1002/glia.20986
[62] Megraw, T.L., Sharkey, J.T., and Nowakowski, R.S. (2011). Cdk5rap2 exposes the centrosomal root of microcephaly syndromes. Trends Cell Biol 21, 470-480 .10.1016/j.tcb.2011.04.007
[63] Miele, L., Miao, H., and Nickoloff, B.J. (2006). NOTCH signaling as a novel cancer therapeutic target. Curr Cancer Drug Targets 6, 313-323 .10.2174/156800906777441771
[64] Mione, M.C., Danevic, C., Boardman, P., Harris, B., and Parnavelas, J.G. (1994). Lineage analysis reveals neurotransmitter (GABA or glutamate) but not calcium-binding protein homogeneity in clonally related cortical neurons. J Neurosci 14, 107-123 .
[65] Miyata, T., Kawaguchi, A., Okano, H., and Ogawa, M. (2001). Asymmetric inheritance of radial glial fibers by cortical neurons. Neuron 31, 727-741 .10.1016/S0896-6273(01)00420-2
[66] Miyata, T., Kawaguchi, A., Saito, K., Kawano, M., Muto, T., and Ogawa, M. (2004). Asymmetric production of surface-dividing and non-surface-dividing cortical progenitor cells. Development 131, 3133-3145 .10.1242/dev.01173
[67] Mizukami, Y., Kohgo, Y., and Chung, D.C. (2007). Hypoxia inducible factor-1 independent pathways in tumor angiogenesis. Clin Cancer Res 13, 5670-5674 .10.1158/1078-0432.CCR-07-0111
[68] Mizutani, K., Yoon, K., Dang, L., Tokunaga, A., and Gaiano, N. (2007). Differential Notch signalling distinguishes neural stem cells from intermediate progenitors. Nature 449, 351-355 .10.1038/nature06090
[69] Niethammer, M., Smith, D.S., Ayala, R., Peng, J.M., Ko, J., Lee, M.S., Morabito, M., and Tsai, L.H. (2000). NUDEL is a novel Cdk5 substrate that associates with LIS1 and cytoplasmic dynein. Neuron 28, 697-711 .10.1016/S0896-6273(00)00147-1
[70] Nieto, M., Monuki, E.S., Tang, H., Imitola, J., Haubst, N., Khoury, S.J., Cunningham, J., Gotz, M., and Walsh, C.A. (2004). Expression of Cux-1 and Cux-2 in the subventricular zone and upper layers II-IV of the cerebral cortex. J Comp Neurol 479, 168-180 .10.1002/cne.20322
[71] Nishide, K., Nakatani, Y., Kiyonari, H., and Kondo, T. (2009). Glioblastoma formation from cell population depleted of Prominin1-expressing cells. PLoS One 4, e6869.10.1371/journal.pone.0006869
[72] Niu, C.S., Li, D.X., Liu, Y.H., Fu, X.M., Tang, S.F., and Li, J. (2011). Expression of NANOG in human gliomas and its relationship with undifferentiated glioma cells. Oncol Rep 26, 593-601 .
[73] Noctor, S.C., Flint, A.C., Weissman, T.A., Dammerman, R.S., and Kriegstein, A.R. (2001). Neurons derived from radial glial cells establish radial units in neocortex. Nature 409, 714-720 .10.1038/35055553
[74] Noctor, S.C., Flint, A.C., Weissman, T.A., Wong, W.S., Clinton, B.K., and Kriegstein, A.R. (2002). Dividing precursor cells of the embryonic cortical ventricular zone have morphological and molecular characteristics of radial glia. J Neurosci 22, 3161-3173 .
[75] Noctor, S.C., Martínez-Cerde?o, V., Ivic, L., and Kriegstein, A.R. (2004). Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases. Nat Neurosci 7, 136-144 .10.1038/nn1172
[76] Noctor, S.C., Martínez-Cerde?o, V., and Kriegstein, A.R. (2007a). Contribution of intermediate progenitor cells to cortical histogenesis. Arch Neurol 64, 639-642 .10.1001/archneur.64.5.639
[77] Noctor, S.C., Martinez-Cerdeno, V., and Kriegstein, A.R. (2007b). Neural stem and progenitor cells in cortical development. Novartis Found Symp 288, 59-73 ; discussion 73-58, 96-58.
[78] Noguera-Troise, I., Daly, C., Papadopoulos, N.J., Coetzee, S., Boland, P., Gale, N.W., Lin, H.C., Yancopoulos, G.D., and Thurston, G. (2006). Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis. Nature 444, 1032-1037 .10.1038/nature05355
[79] Pattison, L., Crow, Y.J., Deeble, V.J., Jackson, A.P., Jafri, H., Rashid, Y., Roberts, E., and Woods, C.G. (2000). A fifth locus for primary autosomal recessive microcephaly maps to chromosome 1q31. Am J Hum Genet 67, 1578-1580 .10.1086/316910
[80] Plate, K.H., Breier, G., Weich, H.A., and Risau, W. (1992). Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature 359, 845-848 .10.1038/359845a0
[81] Price, J., and Thurlow, L. (1988). Cell lineage in the rat cerebral cortex: a study using retroviral-mediated gene transfer. Development 104, 473-482 .
[82] Purow, B.W., Haque, R.M., Noel, M.W., Su, Q., Burdick, M.J., Lee, J., Sundaresan, T., Pastorino, S., Park, J.K., Mikolaenko, I., . (2005). Expression of Notch-1 and its ligands, Delta-like-1 and Jagged-1, is critical for glioma cell survival and proliferation. Cancer Res 65, 2353-2363 .10.1158/0008-5472.CAN-04-1890
[83] Rakic, P. (1978). Neuronal migration and contact guidance in the primate telencephalon. Postgrad Med J 54, 25-40 .
[84] Reardon, D.A., Egorin, M.J., Desjardins, A., Vredenburgh, J.J., Beumer, J.H., Lagattuta, T.F., Gururangan, S., Herndon, J.E. 2nd, Salvado, A.J., and Friedman, H.S. (2009). Phase I pharmacokinetic study of the vascular endothelial growth factor receptor tyrosine kinase inhibitor vatalanib (PTK787) plus imatinib and hydroxyurea for malignant glioma. Cancer 115, 2188-2198 .10.1002/cncr.24213
[85] Reynolds, B.A., Tetzlaff, W., and Weiss, S. (1992). A multipotent EGF-responsive striatal embryonic progenitor cell produces neurons and astrocytes. J Neurosci 12, 4565-4574 .
[86] Ridgway, J., Zhang, G., Wu, Y., Stawicki, S., Liang, W.C., Chanthery, Y., Kowalski, J., Watts, R.J., Callahan, C., Kasman, I., . (2006). Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis. Nature 444, 1083-1087 .10.1038/nature05313
[87] Seidman, K.J., Teng, A.L., Rosenkopf, R., Spilotro, P., and Weyhenmeyer, J.A. (1997). Isolation, cloning and characterization of a putative type-1 astrocyte cell line. Brain Res 753, 18-26 .10.1016/S0006-8993(96)01481-3
[88] Shats, I., Gatza, M.L., Chang, J.T., Mori, S., Wang, J., Rich, J., and Nevins, J.R. (2011). Using a stem cell-based signature to guide therapeutic selection in cancer. Cancer Res 71, 1772-1780 .10.1158/0008-5472.CAN-10-1735
[89] Siebzehnrubl, F.A., Jeske, I., Müller, D., Buslei, R., Coras, R., Hahnen, E., Huttner, H.B., Corbeil, D., Kaesbauer, J., Appl, T., . (2009). Spontaneous in vitro transformation of adult neural precursors into stem-like cancer cells. Brain Pathol 19, 399-408 .10.1111/j.1750-3639.2008.00189.x
[90] Singh, S.K., Clarke, I.D., Terasaki, M., Bonn, V.E., Hawkins, C., Squire, J., and Dirks, P.B. (2003). Identification of a cancer stem cell in human brain tumors. Cancer Res 63, 5821-5828 .
[91] Singh, S.K., Hawkins, C., Clarke, I.D., Squire, J.A., Bayani, J., Hide, T., Henkelman, R.M., Cusimano, M.D., and Dirks, P.B. (2004). Identification of human brain tumour initiating cells. Nature 432, 396-401 .10.1038/nature03128
[92] Smart, I.H., Dehay, C., Giroud, P., Berland, M., and Kennedy, H. (2002). Unique morphological features of the proliferative zones and postmitotic compartments of the neural epithelium giving rise to striate and extrastriate cortex in the monkey. Cereb Cortex 12, 37-53 .10.1093/cercor/12.1.37
[93] Soeda, A., Inagaki, A., Oka, N., Ikegame, Y., Aoki, H., Yoshimura, S., Nakashima, S., Kunisada, T., and Iwama, T. (2008). Epidermal growth factor plays a crucial role in mitogenic regulation of human brain tumor stem cells. J Biol Chem 283, 10958-10966 .10.1074/jbc.M704205200
[94] Sutton, L.N., Phillips, P., and Lange, B. (1992). Midline supratentorial tumors. Neurosurg Clin N Am 3, 821-837 .
[95] Tamamaki, N., Nakamura, K., Okamoto, K., and Kaneko, T. (2001). Radial glia is a progenitor of neocortical neurons in the developing cerebral cortex. Neurosci Res 41, 51-60 .10.1016/S0168-0102(01)00259-0
[96] Tamura, K., Aoyagi, M., Wakimoto, H., Ando, N., Nariai, T., Yamamoto, M., and Ohno, K. (2010). Accumulation of CD133-positive glioma cells after high-dose irradiation by Gamma Knife surgery plus external beam radiation. J Neurosurg 113, 310-318 .10.3171/2010.2.JNS091607
[97] Tarabykin, V., Stoykova, A., Usman, N., and Gruss, P. (2001). Cortical upper layer neurons derive from the subventricular zone as indicated by Svet1 gene expression. Development 128, 1983-1993 .
[98] Tischfield, M.A., Cederquist, G.Y., Gupta, M.L. Jr, and Engle, E.C. (2011). Phenotypic spectrum of the tubulin-related disorders and functional implications of disease-causing mutations. Curr Opin Genet Dev 21, 286-294 .10.1016/j.gde.2011.01.003
[99] Tohyama, T., Lee, V.M., Rorke, L.B., Marvin, M., McKay, R.D., and Trojanowski, J.Q. (1992). Nestin expression in embryonic human neuroepithelium and in human neuroepithelial tumor cells. Lab Invest 66, 303-313 .
[100] Uhrbom, L., Dai, C., Celestino, J.C., Rosenblum, M.K., Fuller, G.N., and Holland, E.C. (2002). Ink4a-Arf loss cooperates with KRas activation in astrocytes and neural progenitors to generate glioblastomas of various morphologies depending on activated Akt. Cancer Res 62, 5551-5558 .
[101] Uhrbom, L., Hesselager, G., Nistér, M., and Westermark, B. (1998). Induction of brain tumors in mice using a recombinant platelet-derived growth factor B-chain retrovirus. Cancer Res 58, 5275-5279 .
[102] Umeshima, H., Hirano, T., and Kengaku, M. (2007). Microtubule- based nuclear movement occurs independently of centrosome positioning in migrating neurons. Proc Natl Acad Sci U S A 104, 16182-16187 .10.1073/pnas.0708047104
[103] Vick, N.A., Lin, M.J., and Bigner, D.D. (1977). The role of the subependymal plate in glial tumorigenesis. Acta Neuropathol 40, 63-71 .10.1007/BF00688574
[104] Wechsler-Reya, R., and Scott, M.P. (2001). The developmental biology of brain tumors. Annu Rev Neurosci 24, 385-428 .10.1146/annurev.neuro.24.1.385
[105] Weissman, T.A., Riquelme, P.A., Ivic, L., Flint, A.C., and Kriegstein, A.R. (2004). Calcium waves propagate through radial glial cells and modulate proliferation in the developing neocortex. Neuron 43, 647-661 .10.1016/j.neuron.2004.08.015
[106] Wells, A., Kassis, J., Solava, J., Turner, T., and Lauffenburger, D.A. (2002). Growth factor-induced cell motility in tumor invasion. Acta Oncol 41, 124-130 .10.1080/028418602753669481
[107] Wu, D.K., and Cepko, C.L. (1993). Development of dopaminergic neurons is insensitive to optic nerve section in the neonatal rat retina. Brain Res Dev Brain Res 74, 253-260 .10.1016/0165-3806(93)90011-X
[108] Yoon, K.J., Koo, B.K., Im, S.K., Jeong, H.W., Ghim, J., Kwon, M.C., Moon, J.S., Miyata, T., and Kong, Y.Y. (2008). Mind bomb 1-expressing intermediate progenitors generate notch signaling to maintain radial glial cells. Neuron 58, 519-531 .10.1016/j.neuron.2008.03.018
[109] Yuan,X., Curtin,J., Xiong,Y., Liu,G., Waschsmann-Hogiu,S., Farkas,D.L., Black,K.L., and Yu,J.S. (2004). Isolation of cancer stem cells from adult glioblastoma multiforme. Oncogene 23, 9392-9400 .10.1038/sj.onc.1208311
[110] Zbinden,M., Duquet, A., Lorente-Trigos, A., Ngwabyt, S.N., Borges, I., and Ruiz i Altaba, A. (2010). NANOG regulates glioma stem cells and is essential in vivo acting in a cross-functional network with GLI1 and p53. EMBO J 29, 2659-2674 .10.1038/emboj.2010.137
[111] Zhang, M., Song, T., Yang, L., Chen, R., Wu, L., Yang, Z., and Fang, J. (2008). Nestin and CD133: valuable stem cell-specific markers for determining clinical outcome of glioma patients. J Exp Clin Cancer Res 27, 85.10.1186/1756-9966-27-85
[112] Zhu, H., Acquaviva, J., Ramachandran, P., Boskovitz, A., Woolfenden, S., Pfannl, R., Bronson, R.T., Chen, J.W., Weissleder, R., Housman, D.E., . (2009). Oncogenic EGFR signaling cooperates with loss of tumor suppressor gene functions in gliomagenesis. Proc Natl Acad Sci U S A 106, 2712-2716 .10.1073/pnas.0813314106
[113] Zimmer, C., Tiveron, M.C., Bodmer, R., and Cremer, H. (2004). Dynamics of Cux2 expression suggests that an early pool of SVZ precursors is fated to become upper cortical layer neurons. Cereb Cortex 14, 1408-1420 .10.1093/cercor/bhh102