Review Special Issues

Neural stem cell derived tumourigenesis

  • Received: 23 November 2014 Accepted: 11 January 2015 Published: 13 January 2015
  • In the developing Drosophila CNS, two pools of neural stem cells, the symmetrically dividing progenitors in the neuroepithelium (NE) and the asymmetrically dividing neuroblasts (NBs) generate the majority of the neurons that make up the adult central nervous system (CNS). The generation of a correct sized brain depends on maintaining the fine balance between neural stem cell self-renewal and differentiation, which are regulated by cell-intrinsic and cell-extrinsic cues. In this review, we will discuss our current understanding of how self-renewal and differentiation are regulated in the two neural stem cell pools, and the consequences of the deregulation of these processes.

    Citation: Francesca Froldi, Milán Szuperák, Louise Y. Cheng. Neural stem cell derived tumourigenesis[J]. AIMS Genetics, 2015, 2(1): 13-24. doi: 10.3934/genet.2015.1.13

    Related Papers:

  • In the developing Drosophila CNS, two pools of neural stem cells, the symmetrically dividing progenitors in the neuroepithelium (NE) and the asymmetrically dividing neuroblasts (NBs) generate the majority of the neurons that make up the adult central nervous system (CNS). The generation of a correct sized brain depends on maintaining the fine balance between neural stem cell self-renewal and differentiation, which are regulated by cell-intrinsic and cell-extrinsic cues. In this review, we will discuss our current understanding of how self-renewal and differentiation are regulated in the two neural stem cell pools, and the consequences of the deregulation of these processes.


    加载中
    [1] Vescovi AL, Galli R, Reynolds BA (2006) Brain tumour stem cells. Nat Rev Cancer 6: 425-436. doi: 10.1038/nrc1889
    [2] Brand AH, Livesey FJ (2011) Neural stem cell biology in vertebrates and invertebrates: more alike than different? Neuron 70: 719-729. doi: 10.1016/j.neuron.2011.05.016
    [3] Egger B, Gold KS, Brand AH (2010) Notch regulates the switch from symmetric to asymmetric neural stem cell division in the Drosophila optic lobe. Development 137: 2981-2987. doi: 10.1242/dev.051250
    [4] Orihara-Ono M, Toriya M, Nakao K, et al. (2011) Developmental Biology. Dev Biol 351: 163-175. doi: 10.1016/j.ydbio.2010.12.044
    [5] Yasugi T, Umetsu D, Murakami S, et al. (2008) Drosophila optic lobe neuroblasts triggered by a wave of proneural gene expression that is negatively regulated by JAK/STAT. Development 135: 1471-1480. doi: 10.1242/dev.019117
    [6] Ngo KT, Wang J, Junker M, et al. (2010) Concomitant requirement for Notch and Jak/Stat signaling during neuro-epithelial differentiation in the Drosophila optic lobe. Dev Biol 346: 284-295. doi: 10.1016/j.ydbio.2010.07.036
    [7] Zhao B, Li L, Lei Q, et al. (2010) The Hippo-YAP pathway in organ size control and tumorigenesis: an updated version. Gene Dev 24: 862-874. doi: 10.1101/gad.1909210
    [8] Halder G, Johnson RL (2011) Hippo signaling: growth control and beyond. Development 138: 9-22. doi: 10.1242/dev.045500
    [9] Yasugi T, Sugie A, Umetsu D, et al. (2010) Coordinated sequential action of EGFR and Notch signaling pathways regulates proneural wave progression in the Drosophila optic lobe. Development 137: 3193-3203. doi: 10.1242/dev.048058
    [10] Reddy BVVG, Rauskolb C, Irvine KD (2010) Influence of fat-hippo and notch signaling on the proliferation and differentiation of Drosophila optic neuroepithelia. Development 137: 2397-2408. doi: 10.1242/dev.050013
    [11] Morante J, Vallejo DM, Desplan C, et al. (2013) Conserved miR-8/miR-200 Defines a Glial Niche that Controls Neuroepithelial Expansion and Neuroblast Transition. Dev Cell 27: 174-187. doi: 10.1016/j.devcel.2013.09.018
    [12] Skeath JB, Thor S (2003) Genetic control of Drosophila nerve cord development. Curr Opin Neurobiol 13: 8-15. doi: 10.1016/S0959-4388(03)00007-2
    [13] Reichert H (2011) Drosophila neural stem cells: cell cycle control of self-renewal, differentiation, and termination in brain development. Results Probl Cell Differ 53: 529-546.
    [14] Prokop A, Technau GM (1991) The origin of postembryonic neuroblasts in the ventral nerve cord of Drosophila melanogaster. Development 111: 79-88.
    [15] Truman JW, Bate M (1988) Spatial and temporal patterns of neurogenesis in the central nervous system of Drosophila melanogaster. Dev Biol 125 145-157.
    [16] Maurange C, Cheng L, Gould AP (2008) Temporal transcription factors and their targets schedule the end of neural proliferation in Drosophila. Cell 133: 891-902. doi: 10.1016/j.cell.2008.03.034
    [17] Homem CCF, Steinmann V, Burkard TR, et al. (2014) Ecdysone and Mediator Change Energy Metabolism to Terminate Proliferationin Drosophila Neural Stem Cells. Cell 158: 874-888. doi: 10.1016/j.cell.2014.06.024
    [18] Bowman SK, Rolland V, Betschinger J, et al. (2008) The tumor suppressors Brat and Numb regulate transit-amplifying neuroblast lineages in Drosophila. Dev Cell 14: 535-546. doi: 10.1016/j.devcel.2008.03.004
    [19] Bello BC, Izergina N, Caussinus E, et al. (2008) Amplification of neural stem cell proliferation by intermediate progenitor cells in Drosophila brain development. Neural Dev 3: 5.
    [20] Homem CCF, Reichardt I, Berger C, et al (2013) Long-term live cell imaging and automated 4D analysis of drosophila neuroblast lineages. PLoS ONE 8: e79588. doi: 10.1371/journal.pone.0079588
    [21] Weng M, Golden KL, Lee C-Y (2010) dFezf/Earmuff maintains the restricted developmental potential of intermediate neural progenitors in Drosophila. Dev Cell 18: 126-135. doi: 10.1016/j.devcel.2009.12.007
    [22] Bayraktar OA, Boone JQ, Drummond ML, et al. (2010) Drosophila type II neuroblast lineages keep Prospero levels low to generate large clones that contribute to the adult brain central complex. Neural Dev 5: 26. doi: 10.1186/1749-8104-5-26
    [23] Chell JM, Brand AH (2010) Nutrition-Responsive Glia Control Exit of Neural Stem Cells from Quiescence. Cell 143: 1161-1173. doi: 10.1016/j.cell.2010.12.007
    [24] Sousa-Nunes R, Yee LL, Gould AP (2011) Fat cells reactivate quiescent neuroblasts via TOR and glial insulin relays in Drosophila. Nature 471: 508-512. doi: 10.1038/nature09867
    [25] Fernández-Hernández I, Rhiner C, Moreno E (2013) Adult neurogenesis in Drosophila. Cell Rep 3: 1857-1865. doi: 10.1016/j.celrep.2013.05.034
    [26] Schober M, Schaefer M, Knoblich JA (1999) Bazooka recruits Inscuteable to orient asymmetric cell divisions in Drosophila neuroblasts. Nature 402: 548-551. doi: 10.1038/990135
    [27] Petronczki M, Knoblich JA (2001) DmPAR-6 directs epithelial polarity and asymmetric cell division of neuroblasts in Drosophila. Nat Cell Biol 3: 43-49. doi: 10.1038/35050550
    [28] Wodarz A, Ramrath A, Grimm A, et al. (2000) Drosophila atypical protein kinase C associates with Bazooka and controls polarity of epithelia and neuroblasts. J Cell Biol 150: 1361-1374. doi: 10.1083/jcb.150.6.1361
    [29] Rolls MM, Albertson R, Shih H-P, et al. (2003) Drosophila aPKC regulates cell polarity and cell proliferation in neuroblasts and epithelia. J Cell Biol 163: 1089-1098. doi: 10.1083/jcb.200306079
    [30] Betschinger J, Mechtler K, Knoblich JA (2003) The Par complex directs asymmetric cell division by phosphorylating the cytoskeletal protein Lgl. Nature 422: 326-330. doi: 10.1038/nature01486
    [31] Schaefer M, Petronczki M, Dorner D, et al. (2001) Heterotrimeric G proteins direct two modes of asymmetric cell division in the Drosophila nervous system. Cell 107: 183-194. doi: 10.1016/S0092-8674(01)00521-9
    [32] Schaefer M, Shevchenko A, Shevchenko A, et al. (2000) A protein complex containing Inscuteable and the Galpha-binding protein Pins orients asymmetric cell divisions in Drosophila. Curr Biol 10: 353-362. doi: 10.1016/S0960-9822(00)00401-2
    [33] Yu F, Morin X, Cai Y, et al. (2000) Analysis of partner of inscuteable, a novel player of Drosophila asymmetric divisions, reveals two distinct steps in inscuteable apical localization. Cell 100: 399-409. doi: 10.1016/S0092-8674(00)80676-5
    [34] Nipper RW, Siller KH, Smith NR, et al. (2007) Galphai generates multiple Pins activation states to link cortical polarity and spindle orientation in Drosophila neuroblasts. Proc Natl Acad Sci USA 104: 14306-14311. doi: 10.1073/pnas.0701812104
    [35] Izumi Y, Ohta N, Hisata K, et al. (2006) Drosophila Pins-binding protein Mud regulates spindle-polarity coupling and centrosome organization. Nat Cell Biol 8: 586-593. doi: 10.1038/ncb1409
    [36] Siller KH, Cabernard C, Doe CQ (2006) The NuMA-related Mud protein binds Pins and regulates spindle orientation in Drosophila neuroblasts. Nat Cell Biol 8: 594-600. doi: 10.1038/ncb1412
    [37] Bowman SK, Neumüller RA, Novatchkova M, et al. (2006) The Drosophila NuMA Homolog Mud regulates spindle orientation in asymmetric cell division. Dev Cell 10: 731-742. doi: 10.1016/j.devcel.2006.05.005
    [38] Siller KH, Doe CQ (2008) Lis1/dynactin regulates metaphase spindle orientation in Drosophila neuroblasts. Dev Biol 319: 1-9. doi: 10.1016/j.ydbio.2008.03.018
    [39] Lee C-Y, Wilkinson BD, Siegrist SE, et al. (2006) Brat is a Miranda cargo protein that promotes neuronal differentiation and inhibits neuroblast self-renewal. Dev Cell 10: 441-449. doi: 10.1016/j.devcel.2006.01.017
    [40] Wang C, Chang KC, Somers G, et al. (2009) Protein phosphatase 2A regulates self-renewal of Drosophila neural stem cells. Development 136: 2287-2296. doi: 10.1242/dev.035758
    [41] Ogawa H, Ohta N, Moon W, et al. (2009) Protein phosphatase 2A negatively regulates aPKC signaling by modulating phosphorylation of Par-6 in Drosophila neuroblast asymmetric divisions. J Cell Sci 122: 3242-3249. doi: 10.1242/jcs.050955
    [42] Chang KC, Garcia-Alvarez G, Somers G, et al. (2010) Interplay between the transcription factor Zif and aPKC regulates neuroblast polarity and self-renewal. Dev Cell 19: 778-785. doi: 10.1016/j.devcel.2010.10.007
    [43] Caussinus E, Gonzalez C (2005) Induction of tumor growth by altered stem-cell asymmetric division in Drosophila melanogaster. Nat Genet 37: 1125-1129. doi: 10.1038/ng1632
    [44] Wang H, Somers GW, Bashirullah A, et al. (2006) Aurora-A acts as a tumor suppressor and regulates self-renewal of Drosophila neuroblasts. Gene Dev 20: 3453-3463. doi: 10.1101/gad.1487506
    [45] Lee C-Y, Andersen RO, Cabernard C, et al. (2006) Drosophila Aurora-A kinase inhibits neuroblast self-renewal by regulating aPKC/Numb cortical polarity and spindle orientation. Gene Dev 20: 3464-3474. doi: 10.1101/gad.1489406
    [46] Wang H, Ouyang Y, Somers WG, et al. (2007) Polo inhibits progenitor self-renewal and regulates Numb asymmetry by phosphorylating Pon. Nature 449: 96-100. doi: 10.1038/nature06056
    [47] Chu-LaGraff Q, Wright DM, McNeil LK, et al. (1991) The prospero gene encodes a divergent homeodomain protein that controls neuronal identity in Drosophila. Development Suppl 2: 79-85.
    [48] Knoblich JA, Jan LY, Jan YN (1995) Asymmetric segregation of Numb and Prospero during cell division. Nature 377: 624-627. doi: 10.1038/377624a0
    [49] Spana EP, Doe CQ (1995) The prospero transcription factor is asymmetrically localized to the cell cortex during neuroblast mitosis in Drosophila. Development 121: 3187-3195.
    [50] Shen CP, Jan LY, Jan YN (1997) Miranda is required for the asymmetric localization of Prospero during mitosis in Drosophila. Cell 90: 449-458. doi: 10.1016/S0092-8674(00)80505-X
    [51] Choksi SP, Southall TD, Bossing T, et al. (2006) Prospero acts as a binary switch between self-renewal and differentiation in Drosophila neural stem cells. Dev Cell 11: 775-789. doi: 10.1016/j.devcel.2006.09.015
    [52] Betschinger J, Mechtler K, Knoblich JA (2006) Asymmetric segregation of the tumor suppressor brat regulates self-renewal in Drosophila neural stem cells. Cell 124: 1241-1253. doi: 10.1016/j.cell.2006.01.038
    [53] Song Y, Lu B (2012) Interaction of Notch signaling modulator Numb with α-Adaptin regulates endocytosis of Notch pathway components and cell fate determination of neural stem cells. J Biol Chem 287: 17716-17728. doi: 10.1074/jbc.M112.360719
    [54] Couturier L, Mazouni K, Schweisguth F (2013) Numb localizes at endosomes and controls the endosomal sorting of notch after asymmetric division in Drosophila. Curr Biol 23: 588-593.
    [55] Lin S, Lai SL, Yu HH, et al. (2009) Lineage-specific effects of Notch/Numb signaling in post-embryonic development of the Drosophila brain. Development 137: 43-51.
    [56] San-Juán BP, Baonza A (2011) The bHLH factor deadpan is a direct target of Notch signaling and regulates neuroblast self-renewal in Drosophila. Dev Biol 352: 70-82. doi: 10.1016/j.ydbio.2011.01.019
    [57] Song Y, Lu B (2011) Regulation of cell growth by Notch signaling and its differential requirement in normal vs. tumor-forming stem cells in Drosophila. Gene Dev 25: 2644-2658.
    [58] Xiao Q, Komori H, Lee C-Y (2012) klumpfuss distinguishes stem cells from progenitor cells during asymmetric neuroblast division. Development 139: 2670-2680. doi: 10.1242/dev.081687
    [59] Zacharioudaki E, Magadi SS, Delidakis C (2012) bHLH-O proteins are crucial for Drosophila neuroblast self-renewal and mediate Notch-induced overproliferation. Development 139: 1258-1269. doi: 10.1242/dev.071779
    [60] Bello B, Reichert H, Hirth F (2006) The brain tumor gene negatively regulates neural progenitor cell proliferation in the larval central brain of Drosophila. Development 133: 2639-2648. doi: 10.1242/dev.02429
    [61] Almeida MS, Bray SJ (2005) Regulation of post-embryonic neuroblasts by Drosophila Grainyhead. Mech Dev 122: 1282-1293. doi: 10.1016/j.mod.2005.08.004
    [62] Berger C, Harzer H, Burkard TR, et al. (2012) FACS purification and transcriptome analysis of drosophila neural stem cells reveals a role for Klumpfuss in self-renewal. Cell Rep 2: 407-418. doi: 10.1016/j.celrep.2012.07.008
    [63] Komori H, Xiao Q, McCartney BM, et al. (2014) Brain tumor specifies intermediate progenitor cell identity by attenuating β-catenin/Armadillo activity. Development 141: 51-62. doi: 10.1242/dev.099382
    [64] Janssens DH, Komori H, Grbac D, et al. (2014) Earmuff restricts progenitor cell potential by attenuating the competence to respond to self-renewal factors. Development 141: 1036-1046. doi: 10.1242/dev.106534
    [65] Koe CT, Li S, Rossi F, et al. (2014) The Brm-HDAC3-Erm repressor complex suppresses dedifferentiation in Drosophila type II neuroblast lineages. Elife 3: e01906.
    [66] Eroglu E, Burkard TR, Jiang Y, et al. (2014) SWI/SNF complex prevents lineage reversion and induces temporal patterning in neural stem cells. Cell 156: 1259-1273. doi: 10.1016/j.cell.2014.01.053
    [67] Janic A, Mendizabal L, Llamazares S, et al. (2010) Ectopic expression of germline genes drives malignant brain tumor growth in Drosophila. Science 330: 1824-1827. doi: 10.1126/science.1195481
    [68] Richter C, Oktaba K, Steinmann J, et al. (2011) The tumour suppressor L(3)mbt inhibits neuroepithelial proliferation and acts on insulator elements. Nat Cell Biol 13: 1029-1039. doi: 10.1038/ncb2306
    [69] Aloia L, Di Stefano B, Di Croce L (2013) Polycomb complexes in stem cells and embryonic development. Development 140: 2525-2534. doi: 10.1242/dev.091553
    [70] Southall TD, Davidson CM, Miller C, et al. (2014)Dedifferentiation of neurons precedes tumor formation in Lola mutants. Dev Cell 28: 685-696.
    [71] Carney TD, Struck AJ, Doe CQ (2013) Midlife crisis encodes a conserved zinc-finger protein required to maintain neuronal differentiation in Drosophila. Development 140: 4155-4164. doi: 10.1242/dev.093781
    [72] Froldi F, Szuperak M, Weng CF, et al. (2015) The transcription factor Nerfin-1 prevents reversion of neurons into neural stem cells. Gene Dev 29 [in press].
    [73] Read RD, Cavenee WK, Furnari FB, et al. (2009) A drosophila model for EGFR-Ras and PI3K-dependent human glioma. PLoS Genet 5: e1000374. doi: 10.1371/journal.pgen.1000374
    [74] Read RD, Fenton TR, Gomez GG, et al. (2013) A Kinome-Wide RNAi Screen in Drosophila Glia Reveals That the RIO Kinases Mediate Cell Proliferation and Survival through TORC2-Akt Signaling in Glioblastoma. PLoS Genet 9: e1003253. doi: 10.1371/journal.pgen.1003253
    [75] Witte HT, Jeibmann A, Klämbt C, et al. (2009) Modeling glioma growth and invasion in Drosophila melanogaster. Neoplasia 11: 882-888. doi: 10.1593/neo.09576
  • Reader Comments
  • © 2015 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

Metrics

Article views(4994) PDF downloads(1073) Cited by(0)

Article outline

Figures and Tables

Figures(3)

/

DownLoad:  Full-Size Img  PowerPoint
Return
Return

Catalog