Notch: an interactive player in neurogenesis and disease

Springer Science and Business Media LLC - Tập 371 - Trang 73-89 - 2017
Runrui Zhang1, Anna Engler1, Verdon Taylor1
1Embryology and Stem Cell Biology, Department of Biomedicine, University of Basel, Basel, Switzerland

Tóm tắt

Notch signaling is evolutionarily conserved from Drosophila to human. It plays critical roles in neural stem cell maintenance and neurogenesis in the embryonic brain as well as in the adult brain. Notch functions greatly depend on careful regulation and cross-talk with other regulatory mechanisms. Deregulation of Notch signaling is involved in many neurodegenerative diseases and brain disorders. Here, we summarize the fundamental role of Notch in neuronal development and specification and discuss how epigenetic regulation and pathway cross-talk contribute to Notch function. In addition, we cover aberrant alterations of Notch signaling in the diseased brain. The aim of this review is to provide an insight into how Notch signaling works in different contexts to control neurogenesis and its potential effects in diagnoses and therapies of neurodegeneration, brain tumors and disorders.

Tài liệu tham khảo

Ables JL, Decarolis NA, Johnson MA, Rivera PD, Gao Z, Cooper DC, Radtke F, Hsieh J, Eisch AJ (2010) Notch1 is required for maintenance of the reservoir of adult hippocampal stem cells. J Neurosci 30(31):10484–10492. doi:10.1523/JNEUROSCI.4721-09.2010 Alcantara Llaguno S, Chen J, Kwon CH, Jackson EL, Li Y, Burns DK, Alvarez-Buylla A, Parada LF (2009) Malignant astrocytomas originate from neural stem/progenitor cells in a somatic tumor suppressor mouse model. Cancer Cell 15(1):45–56. doi:10.1016/j.ccr.2008.12.006 Andersson ER, Lendahl U (2014) Therapeutic modulation of Notch signalling-are we there yet? Nat Rev Drug Discov 13(5):357–378. doi:10.1038/nrd4252 Androutsellis-Theotokis A, Leker RR, Soldner F, Hoeppner DJ, Ravin R, Poser SW, Rueger MA, Bae SK, Kittappa R, McKay RD (2006) Notch signalling regulates stem cell numbers in vitro and in vivo. Nature 442(7104):823–826. doi:10.1038/nature04940 Arboleda-Velasquez JF, Manent J, Lee JH, Tikka S, Ospina C, Vanderburg CR, Frosch MP, Rodriguez-Falcon M, Villen J, Gygi S, Lopera F, Kalimo H, Moskowitz MA, Ayata C, Louvi A, Artavanis-Tsakonas S (2011) Hypomorphic Notch 3 alleles link Notch signaling to ischemic cerebral small-vessel disease. Proc Natl Acad Sci U S A 108(21):E128–E135. doi:10.1073/pnas.1101964108 Arboleda-Velasquez JF, Zhou Z, Shin HK, Louvi A, Kim HH, Savitz SI, Liao JK, Salomone S, Ayata C, Moskowitz MA, Artavanis-Tsakonas S (2008) Linking Notch signaling to ischemic stroke. Proc Natl Acad Sci U S A 105(12):4856–4861. doi:10.1073/pnas.0709867105 Artavanis-Tsakonas S, Muskavitch MA, Yedvobnick B (1983) Molecular cloning of Notch, a locus affecting neurogenesis in Drosophila melanogaster. Proc Natl Acad Sci U S A 80(7):1977–1981 Artavanis-Tsakonas S, Rand MD, Lake RJ (1999) Notch signaling: cell fate control and signal integration in development. Science 284(5415):770–776 Bai G, Sheng N, Xie Z, Bian W, Yokota Y, Benezra R, Kageyama R, Guillemot F, Jing N (2007) Id sustains Hes1 expression to inhibit precocious neurogenesis by releasing negative autoregulation of Hes1. Dev Cell 13(2):283–297. doi:10.1016/j.devcel.2007.05.014 Baik SH, Fane M, Park JH, Cheng YL, Yang-Wei Fann D, Yun UJ, Choi Y, Park JS, Chai BH, Park JS, Back SH, Jeong JI, Jang YJ, Bahn G, Lee JY, Li YI, Sobey CG, Uchida T, Park JH, Kim HT, Tang SC, Arumugam TV, Jo DG (2015) Pin1 promotes neuronal death in stroke by stabilizing Notch intracellular domain. Ann Neurol 77(3):504–516. doi:10.1002/ana.24347 Basak O, Giachino C, Fiorini E, Macdonald HR, Taylor V (2012) Neurogenic subventricular zone stem/progenitor cells are Notch1-dependent in their active but not quiescent state. J Neurosci 32(16):5654–5666. doi:10.1523/JNEUROSCI.0455-12.2012 Berezovska O, McLean P, Knowles R, Frosh M, Lu FM, Lux SE, Hyman BT (1999) Notch1 inhibits neurite outgrowth in postmitotic primary neurons. Neuroscience 93(2):433–439 Berezovska O, Xia MQ, Hyman BT (1998) Notch is expressed in adult brain, is coexpressed with presenilin-1, and is altered in Alzheimer disease. J Neuropathol Exp Neurol 57(8):738–745 Bertrand N, Castro DS, Guillemot F (2002) Proneural genes and the specification of neural cell types. Nat Rev Neurosci 3(7):517–530. doi:10.1038/nrn874 Bigas A, Espinosa L (2012) Hematopoietic stem cells: to be or Notch to be. Blood 119(14):3226–3235. doi:10.1182/blood-2011-10-355826 Bonev B, Pisco A, Papalopulu N (2011) MicroRNA-9 reveals regional diversity of neural progenitors along the anterior-posterior axis. Dev Cell 20(1):19–32. doi:10.1016/j.devcel.2010.11.018 Bonev B, Stanley P, Papalopulu N (2012) MicroRNA-9 modulates Hes1 ultradian oscillations by forming a double-negative feedback loop. Cell Rep 2(1):10–18. doi:10.1016/j.celrep.2012.05.017 Borggrefe T, Oswald F (2009) The Notch signaling pathway: transcriptional regulation at Notch target genes. Cell Mol Life Sci 66(10):1631–1646. doi:10.1007/s00018-009-8668-7 Brandt MD, Maass A, Kempermann G, Storch A (2010) Physical exercise increases Notch activity, proliferation and cell cycle exit of type-3 progenitor cells in adult hippocampal neurogenesis. Eur J Neurosci 32(8):1256–1264. doi:10.1111/j.1460-9568.2010.07410.x Brou C, Logeat F, Gupta N, Bessia C, LeBail O, Doedens JR, Cumano A, Roux P, Black RA, Israel A (2000) A novel proteolytic cleavage involved in Notch signaling: the role of the disintegrin-metalloprotease TACE. Mol Cell 5(2):207–216 Cancer Genome Atlas Research N, Brat DJ, Verhaak RG, Aldape KD, Yung WK et al (2015) Comprehensive, integrative genomic analysis of diffuse lower-grade Gliomas. N Engl J Med 372(26):2481–2498. doi:10.1056/NEJMoa1402121 Cao X, Pfaff SL, Gage FH (2008) YAP regulates neural progenitor cell number via the TEA domain transcription factor. Genes Dev 22(23):3320–3334. doi:10.1101/gad.1726608 Castro DS, Skowronska-Krawczyk D, Armant O, Donaldson IJ, Parras C, Hunt C, Critchley JA, Nguyen L, Gossler A, Gottgens B, Matter JM, Guillemot F (2006) Proneural bHLH and Brn proteins coregulate a neurogenic program through cooperative binding to a conserved DNA motif. Dev Cell 11(6):831–844. doi:10.1016/j.devcel.2006.10.006 Charles N, Ozawa T, Squatrito M, Bleau AM, Brennan CW, Hambardzumyan D, Holland EC (2010) Perivascular nitric oxide activates notch signaling and promotes stem-like character in PDGF-induced glioma cells. Cell Stem Cell 6(2):141–152. doi:10.1016/j.stem.2010.01.001 Chen CD, Oh SY, Hinman JD, Abraham CR (2006) Visualization of APP dimerization and APP-Notch2 heterodimerization in living cells using bimolecular fluorescence complementation. J Neurochem 97(1):30–43. doi:10.1111/j.1471-4159.2006.03705.x Chen J, Li Y, Yu TS, McKay RM, Burns DK, Kernie SG, Parada LF (2012) A restricted cell population propagates glioblastoma growth after chemotherapy. Nature 488(7412):522–526. doi:10.1038/nature11287 Chen J, Zacharek A, Li A, Cui X, Roberts C, Lu M, Chopp M (2008) Atorvastatin promotes presenilin-1 expression and Notch1 activity and increases neural progenitor cell proliferation after stroke. Stroke 39(1):220–226. doi:10.1161/STROKEAHA.107.490946 Chi Z, Zhang J, Tokunaga A, Harraz MM, Byrne ST, Dolinko A, Xu J, Blackshaw S, Gaiano N, Dawson TM, Dawson VL (2012) Botch promotes neurogenesis by antagonizing Notch. Dev Cell 22(4):707–720. doi:10.1016/j.devcel.2012.02.011 Cho KO, Lybrand ZR, Ito N, Brulet R, Tafacory F, Zhang L, Good L, Ure K, Kernie SG, Birnbaum SG, Scharfman HE, Eisch AJ, Hsieh J (2015) Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline. Nat Commun 6:6606. doi:10.1038/ncomms7606 Clevers H, Loh KM, Nusse R (2014) Stem cell signaling. An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control. Science 346(6205):1248012. doi:10.1126/science.1248012 Coolen M, Thieffry D, Drivenes O, Becker TS, Bally-Cuif L (2012) miR-9 controls the timing of neurogenesis through the direct inhibition of antagonistic factors. Dev Cell 22(5):1052–1064. doi:10.1016/j.devcel.2012.03.003 Costa RM, Honjo T, Silva AJ (2003) Learning and memory deficits in Notch mutant mice. Curr Biol 13(15):1348–1354 Coumailleau F, Furthauer M, Knoblich JA, Gonzalez-Gaitan M (2009) Directional Delta and Notch trafficking in Sara endosomes during asymmetric cell division. Nature 458(7241):1051–1055. doi:10.1038/nature07854 Couturier L, Vodovar N, Schweisguth F (2012) Endocytosis by numb breaks Notch symmetry at cytokinesis. Nat Cell Biol 14(2):131–139. doi:10.1038/ncb2419 Cunliffe VT (2004) Histone deacetylase 1 is required to repress Notch target gene expression during zebrafish neurogenesis and to maintain the production of motoneurones in response to hedgehog signalling. Development 131(12):2983–2995. doi:10.1242/dev.01166 de la Pompa JL, Wakeham A, Correia KM, Samper E, Brown S, Aguilera RJ, Nakano T, Honjo T, Mak TW, Rossant J, Conlon RA (1997) Conservation of the Notch signalling pathway in mammalian neurogenesis. Development 124(6):1139–1148 De Strooper B, Iwatsubo T, Wolfe MS (2012) Presenilins and gamma-secretase: structure, function, and role in Alzheimer disease. Cold Spring Harbor Perspect Med 2(1):a006304. doi:10.1101/cshperspect.a006304 Donoviel DB, Hadjantonakis AK, Ikeda M, Zheng H, Hyslop PS, Bernstein A (1999) Mice lacking both presenilin genes exhibit early embryonic patterning defects. Genes Dev 13(21):2801–2810 Ehm O, Goritz C, Covic M, Schaffner I, Schwarz TJ, Karaca E, Kempkes B, Kremmer E, Pfrieger FW, Espinosa L, Bigas A, Giachino C, Taylor V, Frisen J, Lie DC (2010) RBPJkappa-dependent signaling is essential for long-term maintenance of neural stem cells in the adult hippocampus. J Neurosci 30(41):13794–13807. doi:10.1523/JNEUROSCI.1567-10.2010 El Hindy N, Keyvani K, Pagenstecher A, Dammann P, Sandalcioglu IE, Sure U, Zhu Y (2013) Implications of Dll4-Notch signaling activation in primary glioblastoma multiforme. Neuro-Oncology 15(10):1366–1378. doi:10.1093/neuonc/not071 Elliott RC, Khademi S, Pleasure SJ, Parent JM, Lowenstein DH (2001) Differential regulation of basic helix-loop-helix mRNAs in the dentate gyrus following status epilepticus. Neuroscience 106(1):79–88 Fan X, Khaki L, Zhu TS, Soules ME, Talsma CE, Gul N, Koh C, Zhang J, Li YM, Maciaczyk J, Nikkhah G, Dimeco F, Piccirillo S, Vescovi AL, Eberhart CG (2010) NOTCH pathway blockade depletes CD133-positive glioblastoma cells and inhibits growth of tumor neurospheres and xenografts. Stem Cells 28(1):5–16. doi:10.1002/stem.254 Fan X, Mikolaenko I, Elhassan I, Ni X, Wang Y, Ball D, Brat DJ, Perry A, Eberhart CG (2004) Notch1 and notch2 have opposite effects on embryonal brain tumor growth. Cancer Res 64(21):7787–7793. doi:10.1158/0008-5472.CAN-04-1446 Farnsworth DR, Bayraktar OA, Doe CQ (2015) Aging neural progenitors lose competence to respond to Mitogenic Notch signaling. Curr Biol 25(23):3058–3068. doi:10.1016/j.cub.2015.10.027 Fineberg SK, Datta P, Stein CS, Davidson BL (2012) MiR-34a represses Numbl in murine neural progenitor cells and antagonizes neuronal differentiation. PLoS ONE 7(6):e38562. doi:10.1371/journal.pone.0038562 Fortini ME (2009) Notch signaling: the core pathway and its posttranslational regulation. Dev Cell 16(5):633–647. doi:10.1016/j.devcel.2009.03.010 Gaiano N, Fishell G (2002) The role of notch in promoting glial and neural stem cell fates. Annu Rev Neurosci 25:471–490. doi:10.1146/annurev.neuro.25.030702.130823 Giachino C, Basak O, Lugert S, Knuckles P, Obernier K, Fiorelli R, Frank S, Raineteau O, Alvarez-Buylla A, Taylor V (2014) Molecular diversity subdivides the adult forebrain neural stem cell population. Stem Cells 32(1):70–84. doi:10.1002/stem.1520 Giachino C, Boulay JL, Ivanek R, Alvarado A, Tostado C, Lugert S, Tchorz J, Coban M, Mariani L, Bettler B, Lathia J, Frank S, Pfister S, Kool M, Taylor V (2015) A tumor suppressor function for Notch signaling in forebrain tumor subtypes. Cancer Cell 28(6):730–742. doi:10.1016/j.ccell.2015.10.008 Gobeske KT, Das S, Bonaguidi MA, Weiss C, Radulovic J, Disterhoft JF, Kessler JA (2009) BMP signaling mediates effects of exercise on hippocampal neurogenesis and cognition in mice. PLoS ONE 4(10):e7506. doi:10.1371/journal.pone.0007506 Gotte M, Greve B, Kelsch R, Muller-Uthoff H, Weiss K, Kharabi Masouleh B, Sibrowski W, Kiesel L, Buchweitz O (2011) The adult stem cell marker Musashi-1 modulates endometrial carcinoma cell cycle progression and apoptosis via Notch-1 and p21WAF1/CIP1. Int J Cancer 129(8):2042–2049. doi:10.1002/ijc.25856 Gratton MO, Torban E, Jasmin SB, Theriault FM, German MS, Stifani S (2003) Hes6 promotes cortical neurogenesis and inhibits Hes1 transcription repression activity by multiple mechanisms. Mol Cell Biol 23(19):6922–6935 Guenther MG, Barak O, Lazar MA (2001) The SMRT and N-CoR corepressors are activating cofactors for histone deacetylase 3. Mol Cell Biol 21(18):6091–6101 Haines N, Irvine KD (2003) Glycosylation regulates Notch signalling. Nat Rev Mol Cell Biol 4(10):786–797. doi:10.1038/nrm1228 Hansson EM, Lendahl U, Chapman G (2004) Notch signaling in development and disease. Semin Cancer Biol 14(5):320–328. doi:10.1016/j.semcancer.2004.04.011 Hardy J, Allsop D (1991) Amyloid deposition as the central event in the aetiology of Alzheimer’s disease. Trends Pharmacol Sci 12(10):383–388 Hatakeyama J, Bessho Y, Katoh K, Ookawara S, Fujioka M, Guillemot F, Kageyama R (2004) Hes genes regulate size, shape and histogenesis of the nervous system by control of the timing of neural stem cell differentiation. Development 131(22):5539–5550. doi:10.1242/dev.01436 Hattori S, Hashimoto R, Miyakawa T, Yamanaka H, Maeno H, Wada K, Kunugi H (2007) Enriched environments influence depression-related behavior in adult mice and the survival of newborn cells in their hippocampi. Behav Brain Res 180(1):69–76. doi:10.1016/j.bbr.2007.02.036 Hirabayashi Y, Itoh Y, Tabata H, Nakajima K, Akiyama T, Masuyama N, Gotoh Y (2004) The Wnt/beta-catenin pathway directs neuronal differentiation of cortical neural precursor cells. Development 131(12):2791–2801. doi:10.1242/dev.01165 Hisahara S, Chiba S, Matsumoto H, Tanno M, Yagi H, Shimohama S, Sato M, Horio Y (2008) Histone deacetylase SIRT1 modulates neuronal differentiation by its nuclear translocation. Proc Natl Acad Sci U S A 105(40):15599–15604. doi:10.1073/pnas.0800612105 Hitoshi S, Ishino Y, Kumar A, Jasmine S, Tanaka KF, Kondo T, Kato S, Hosoya T, Hotta Y, Ikenaka K (2011) Mammalian Gcm genes induce Hes5 expression by active DNA demethylation and induce neural stem cells. Nat Neurosci 14(8):957–964. doi:10.1038/nn.2875 Hoeck JD, Jandke A, Blake SM, Nye E, Spencer-Dene B, Brandner S, Behrens A (2010) Fbw7 controls neural stem cell differentiation and progenitor apoptosis via Notch and c-Jun. Nat Neurosci 13(11):1365–1372. doi:10.1038/nn.2644 Honjo T (1996) The shortest path from the surface to the nucleus: RBP-J kappa/Su(H) transcription factor. Genes Cells: Devoted Mol Cell Mech 1(1):1–9 Hsieh J, Gage FH (2004) Epigenetic control of neural stem cell fate. Curr Opin Genet Dev 14(5):461–469. doi:10.1016/j.gde.2004.07.006 Imayoshi I, Isomura A, Harima Y, Kawaguchi K, Kori H, Miyachi H, Fujiwara T, Ishidate F, Kageyama R (2013) Oscillatory control of factors determining multipotency and fate in mouse neural progenitors. Science 342(6163):1203–1208. doi:10.1126/science.1242366 Imayoshi I, Kageyama R (2011) The role of Notch signaling in adult neurogenesis. Mol Neurobiol 44(1):7–12. doi:10.1007/s12035-011-8186-0 Imayoshi I, Sakamoto M, Yamaguchi M, Mori K, Kageyama R (2010) Essential roles of Notch signaling in maintenance of neural stem cells in developing and adult brains. J Neurosci 30(9):3489–3498. doi:10.1523/JNEUROSCI.4987-09.2010 Imayoshi I, Shimogori T, Ohtsuka T, Kageyama R (2008) Hes genes and neurogenin regulate non-neural versus neural fate specification in the dorsal telencephalic midline. Development 135(15):2531–2541. doi:10.1242/dev.021535 Jessberger S, Gage FH (2008) Stem-cell-associated structural and functional plasticity in the aging hippocampus. Psychol Aging 23(4):684–691. doi:10.1037/a0014188 Jessberger S, Parent JM (2015) Epilepsy and adult neurogenesis. Cold Spring Harb Perspect Biol 7(12). doi:10.1101/cshperspect.a020677 Jessberger S, Zhao C, Toni N, Clemenson GD, Li Y, Gage FH (2007) Seizure-associated, aberrant neurogenesis in adult rats characterized with retrovirus-mediated cell labeling. J Neurosci 27:9400–9407. doi:10.1523/jneurosci.2002-07 Joutel A, Corpechot C, Ducros A, Vahedi K, Chabriat H, Mouton P, Alamowitch S, Domenga V, Cecillion M, Marechal E, Maciazek J, Vayssiere C, Cruaud C, Cabanis EA, Ruchoux MM, Weissenbach J, Bach JF, Bousser MG, Tournier-Lasserve E (1996) Notch3 mutations in CADASIL, a hereditary adult-onset condition causing stroke and dementia. Nature 383(6602):707–710. doi:10.1038/383707a0 Kageyama R, Ohtsuka T, Kobayashi T (2007) The Hes gene family: repressors and oscillators that orchestrate embryogenesis. Development 134(7):1243–1251. doi:10.1242/dev.000786 Kageyama R, Shimojo H, Imayoshi I (2015) Dynamic expression and roles of Hes factors in neural development. Cell Tissue Res 359(1):125–133. doi:10.1007/s00441-014-1888-7 Kao HY, Ordentlich P, Koyano-Nakagawa N, Tang Z, Downes M, Kintner CR, Evans RM, Kadesch T (1998) A histone deacetylase corepressor complex regulates the Notch signal transduction pathway. Genes Dev 12(15):2269–2277 Kawai T, Takagi N, Nakahara M, Takeo S (2005) Changes in the expression of Hes5 and Mash1 mRNA in the adult rat dentate gyrus after transient forebrain ischemia. Neurosci Lett 380(1–2):17–20. doi:10.1016/j.neulet.2005.01.005 Kempermann G (2015) Activity dependency and aging in the regulation of adult neurogenesis. Cold Spring Harb Perspect Biol 7(11). doi:10.1101/cshperspect.a018929 Kim DY, Hwang I, Muller FL, Paik JH (2015) Functional regulation of FoxO1 in neural stem cell differentiation. Cell Death Differ 22(12):2034–2045. doi:10.1038/cdd.2015.123 Kim M, Park YK, Kang TW, Lee SH, Rhee YH, Park JL, Kim HJ, Lee D, Lee D, Kim SY, Kim YS (2014) Dynamic changes in DNA methylation and hydroxymethylation when hES cells undergo differentiation toward a neuronal lineage. Hum Mol Genet 23(3):657–667. doi:10.1093/hmg/ddt453 Kitamura T, Kitamura YI, Funahashi Y, Shawber CJ, Castrillon DH, Kollipara R, DePinho RA, Kitajewski J, Accili D (2007) A Foxo/Notch pathway controls myogenic differentiation and fiber type specification. J Clin Invest 117(9):2477–2485. doi:10.1172/JCI32054 Koch U, Lehal R, Radtke F (2013) Stem cells living with a Notch. Development 140(4):689–704. doi:10.1242/dev.080614 Komiya Y, Habas R (2008) Wnt signal transduction pathways. Organ 4(2):68–75 Kopan R, Ilagan MX (2009) The canonical Notch signaling pathway: unfolding the activation mechanism. Cell 137(2):216–233. doi:10.1016/j.cell.2009.03.045 Kouzarides T (2007) Chromatin modifications and their function. Cell 128(4):693–705. doi:10.1016/j.cell.2007.02.005 Kressmann S, Campos C, Castanon I, Furthauer M, Gonzalez-Gaitan M (2015) Directional Notch trafficking in Sara endosomes during asymmetric cell division in the spinal cord. Nat Cell Biol 17(3):333–339. doi:10.1038/ncb3119 Kuhn HG, Dickinson-Anson H, Gage FH (1996) Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci 16(6):2027–2033 Kurooka H, Honjo T (2000) Functional interaction between the mouse notch1 intracellular region and histone acetyltransferases PCAF and GCN5. J Biol Chem 275(22):17211–17220. doi:10.1074/jbc.M000909200 Kuwabara T, Hsieh J, Muotri A, Yeo G, Warashina M, Lie DC, Moore L, Nakashima K, Asashima M, Gage FH (2009) Wnt-mediated activation of NeuroD1 and retro-elements during adult neurogenesis. Nat Neurosci 12(9):1097–1105. doi:10.1038/nn.2360 Kyriazis GA, Wei Z, Vandermey M, Jo DG, Xin O, Mattson MP, Chan SL (2008) Numb endocytic adapter proteins regulate the transport and processing of the amyloid precursor protein in an isoform-dependent manner: implications for Alzheimer disease pathogenesis. J Biol Chem 283(37):25492–25502. doi:10.1074/jbc.M802072200 LaVoie MJ, Selkoe DJ (2003) The Notch ligands, Jagged and Delta, are sequentially processed by alpha-secretase and presenilin/gamma-secretase and release signaling fragments. J Biol Chem 278(36):34427–34437. doi:10.1074/jbc.M302659200 Li Y, Lei L, Irvine KD, Baker NE (2003) Notch activity in neural cells triggered by a mutant allele with altered glycosylation. Development 130(13):2829–2840 Liau BB, Sievers C, Donohue LK, Gillespie SM, Flavahan WA, Miller TE, Venteicher AS, Hebert CH, Carey CD, Rodig SJ, Shareef SJ, Najm FJ, van Galen P, Wakimoto H, Cahill DP, Rich JN, Aster JC, Suva ML, Patel AP, Bernstein BE (2017) Adaptive chromatin remodeling drives glioblastoma stem cell plasticity and drug tolerance. Cell Stem Cell 20(2):233–246 e237. doi:10.1016/j.stem.2016.11.003 Lim DA, Tramontin AD, Trevejo JM, Herrera DG, Garcia-Verdugo JM, Alvarez-Buylla A (2000) Noggin antagonizes BMP signaling to create a niche for adult neurogenesis. Neuron 28(3):713–726 Liu C, Sage JC, Miller MR, Verhaak RG, Hippenmeyer S, Vogel H, Foreman O, Bronson RT, Nishiyama A, Luo L, Zong H (2011a) Mosaic analysis with double markers reveals tumor cell of origin in glioma. Cell 146(2):209–221. doi:10.1016/j.cell.2011.06.014 Liu C, Teng ZQ, Santistevan NJ, Szulwach KE, Guo W, Jin P, Zhao X (2010a) Epigenetic regulation of miR-184 by MBD1 governs neural stem cell proliferation and differentiation. Cell Stem Cell 6(5):433–444. doi:10.1016/j.stem.2010.02.017 Liu HK, Wang Y, Belz T, Bock D, Takacs A, Radlwimmer B, Barbus S, Reifenberger G, Lichter P, Schutz G (2010b) The nuclear receptor tailless induces long-term neural stem cell expansion and brain tumor initiation. Genes Dev 24(7):683–695. doi:10.1101/gad.560310 Liu XS, Chopp M, Zhang RL, Tao T, Wang XL, Kassis H, Hozeska-Solgot A, Zhang L, Chen C, Zhang ZG (2011b) MicroRNA profiling in subventricular zone after stroke: MiR-124a regulates proliferation of neural progenitor cells through Notch signaling pathway. PLoS ONE 6(8):e23461. doi:10.1371/journal.pone.0023461 Louvi A, Artavanis-Tsakonas S (2012) Notch and disease: a growing field. Semin Cell Dev Biol 23(4):473–480. doi:10.1016/j.semcdb.2012.02.005 Lugert S, Basak O, Knuckles P, Haussler U, Fabel K, Gotz M, Haas CA, Kempermann G, Taylor V, Giachino C (2010) Quiescent and active hippocampal neural stem cells with distinct morphologies respond selectively to physiological and pathological stimuli and aging. Cell Stem Cell 6(5):445–456. doi:10.1016/j.stem.2010.03.017 Lütolf S (2002) Notch1 is required for neuronal and glia differentiation in the cerebellum. Development 129:373–385 Lyden D, Young AZ, Zagzag D, Yan W, Gerald W, O’Reilly R, Bader BL, Hynes RO, Zhuang Y, Manova K, Benezra R (1999) Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts. Nature 401(6754):670–677. doi:10.1038/44334 Ma DK, Marchetto MC, Guo JU, Ming GL, Gage FH, Song H (2010) Epigenetic choreographers of neurogenesis in the adult mammalian brain. Nat Neurosci 13(11):1338–1344. doi:10.1038/nn.2672 Magnusson JP, Goritz C, Tatarishvili J, Dias DO, Smith EM, Lindvall O, Kokaia Z, Frisen J (2014) A latent neurogenic program in astrocytes regulated by Notch signaling in the mouse. Science 346(6206):237–241. doi:10.1126/science.346.6206.237 Manderfield LJ, Aghajanian H, Engleka KA, Lim LY, Liu F, Jain R, Li L, Olson EN, Epstein JA (2015) Hippo signaling is required for Notch-dependent smooth muscle differentiation of neural crest. Development 142(17):2962–2971. doi:10.1242/dev.125807 Masamizu Y, Ohtsuka T, Takashima Y, Nagahara H, Takenaka Y, Yoshikawa K, Okamura H, Kageyama R (2006) Real-time imaging of the somite segmentation clock: revelation of unstable oscillators in the individual presomitic mesoderm cells. Proc Natl Acad Sci U S A 103(5):1313–1318. doi:10.1073/pnas.0508658103 Matsumoto A, Onoyama I, Sunabori T, Kageyama R, Okano H, Nakayama KI (2011) Fbxw7-dependent degradation of Notch is required for control of "stemness" and neuronal-glial differentiation in neural stem cells. J Biol Chem 286(15):13754–13764. doi:10.1074/jbc.M110.194936 Mira H, Andreu Z, Suh H, Lie DC, Jessberger S, Consiglio A, San Emeterio J, Hortiguela R, Marques-Torrejon MA, Nakashima K, Colak D, Gotz M, Farinas I, Gage FH (2010) Signaling through BMPR-IA regulates quiescence and long-term activity of neural stem cells in the adult hippocampus. Cell Stem Cell 7(1):78–89. doi:10.1016/j.stem.2010.04.016 Miranda CJ, Braun L, Jiang Y, Hester ME, Zhang L, Riolo M, Wang H, Rao M, Altura RA, Kaspar BK (2012) Aging brain microenvironment decreases hippocampal neurogenesis through Wnt-mediated survivin signaling. Aging Cell 11(3):542–552. doi:10.1111/j.1474-9726.2012.00816.x Miyazono K, Maeda S, Imamura T (2005) BMP receptor signaling: transcriptional targets, regulation of signals, and signaling cross-talk. Cytokine Growth Factor Rev 16(3):251–263. doi:10.1016/j.cytogfr.2005.01.009 Mizutani K, Yoon K, Dang L, Tokunaga A, Gaiano N (2007) Differential Notch signalling distinguishes neural stem cells from intermediate progenitors. Nature 449(7160):351–355. doi:10.1038/nature06090 Mo JS, Park HW, Guan KL (2014) The Hippo signaling pathway in stem cell biology and cancer. EMBO Rep 15(6):642–656. doi:10.15252/embr.201438638 Molofsky AV, Pardal R, Iwashita T, Park IK, Clarke MF, Morrison SJ (2003) Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature 425(6961):962–967. doi:10.1038/nature02060 Molofsky AV, Slutsky SG, Joseph NM, He S, Pardal R, Krishnamurthy J, Sharpless NE, Morrison SJ (2006) Increasing p16INK4a expression decreases forebrain progenitors and neurogenesis during ageing. Nature 443(7110):448–452. doi:10.1038/nature05091 Mulligan P, Yang F, Di Stefano L, Ji JY, Ouyang J, Nishikawa JL, Toiber D, Kulkarni M, Wang Q, Najafi-Shoushtari SH, Mostoslavsky R, Gygi SP, Gill G, Dyson NJ, Naar AM (2011) A SIRT1-LSD1 corepressor complex regulates Notch target gene expression and development. Mol Cell 42(5):689–699. doi:10.1016/j.molcel.2011.04.020 Mumm JS, Kopan R (2000) Notch signaling: from the outside in. Dev Biol 228(2):151–165. doi:10.1006/dbio.2000.9960 Namihira M, Kohyama J, Semi K, Sanosaka T, Deneen B, Taga T, Nakashima K (2009) Committed neuronal precursors confer astrocytic potential on residual neural precursor cells. Dev Cell 16(2):245–255. doi:10.1016/j.devcel.2008.12.014 Nyfeler Y, Kirch RD, Mantei N, Leone DP, Radtke F, Suter U, Taylor V (2005) Jagged1 signals in the postnatal subventricular zone are required for neural stem cell self-renewal. EMBO J 24:3504–3515 O’Brien RJ, Wong PC (2011) Amyloid precursor protein processing and Alzheimer’s disease. Annu Rev Neurosci 34:185–204. doi:10.1146/annurev-neuro-061010-113613 Ohtsuka T, Ishibashi M, Gradwohl G, Nakanishi S, Guillemot F, Kageyama R (1999) Hes1 and Hes5 as notch effectors in mammalian neuronal differentiation. EMBO J 18(8):2196–2207. doi:10.1093/emboj/18.8.2196 Oswald F, Kostezka U, Astrahantseff K, Bourteele S, Dillinger K, Zechner U, Ludwig L, Wilda M, Hameister H, Knochel W, Liptay S, Schmid RM (2002) SHARP is a novel component of the Notch/RBP-Jkappa signalling pathway. EMBO J 21(20):5417–5426 Oswald F, Tauber B, Dobner T, Bourteele S, Kostezka U, Adler G, Liptay S, Schmid RM (2001) p300 acts as a transcriptional coactivator for mammalian Notch-1. Mol Cell Biol 21(22):7761–7774. doi:10.1128/MCB.21.22.7761-7774.2001 Oswald F, Winkler M, Cao Y, Astrahantseff K, Bourteele S, Knochel W, Borggrefe T (2005) RBP-Jkappa/SHARP recruits CtIP/CtBP corepressors to silence Notch target genes. Mol Cell Biol 25(23):10379–10390. doi:10.1128/MCB.25.23.10379-10390.2005 Parent JM, Yu TW, Leibowitz RT, Geschwind DH, Sloviter RS, Lowenstein DH (1997) Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J Neurosci 17(10):3727–3738 Parks AL, Klueg KM, Stout JR, Muskavitch MA (2000) Ligand endocytosis drives receptor dissociation and activation in the Notch pathway. Development 127(7):1373–1385 Patterson M, Gaeta X, Loo K, Edwards M, Smale S, Cinkornpumin J, Xie Y, Listgarten J, Azghadi S, Douglass SM, Pellegrini M, Lowry WE (2014) Let-7 miRNAs can act through notch to regulate human gliogenesis. Stem Cell Rep 3(5):758–773. doi:10.1016/j.stemcr.2014.08.015 Purow BW, Haque RM, Noel MW, Su Q, Burdick MJ, Lee J, Sundaresan T, Pastorino S, Park JK, Mikolaenko I, Maric D, Eberhart CG, Fine HA (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(6):2353–2363. doi:10.1158/0008-5472.CAN-04-1890 Qu Q, Sun G, Murai K, Ye P, Li W, Asuelime G, Cheung YT, Shi Y (2013) Wnt7a regulates multiple steps of neurogenesis. Mol Cell Biol 33(13):2551–2559. doi:10.1128/MCB.00325-13 Rani N, Nowakowski TJ, Zhou H, Godshalk SE, Lisi V, Kriegstein AR, Kosik KS (2016) A primate lncRNA mediates Notch signaling during neuronal development by sequestering miRNA. Neuron 90(6):1174–1188. doi:10.1016/j.neuron.2016.05.005 Ray WJ, Yao M, Nowotny P, Mumm J, Zhang W, Wu JY, Kopan R, Goate AM (1999) Evidence for a physical interaction between presenilin and Notch. Proc Natl Acad Sci U S A 96(6):3263–3268 Rebay I, Fleming RJ, Fehon RG, Cherbas L, Cherbas P, Artavanis-Tsakonas S (1991) Specific EGF repeats of Notch mediate interactions with Delta and Serrate: implications for Notch as a multifunctional receptor. Cell 67(4):687–699 Redmond L, Ghosh A (2001) The role of Notch and rho GTPase signaling in the control of dendritic development. Curr Opin Neurobiol 11(1):111–117 Rheinbay E, Suva ML, Gillespie SM, Wakimoto H, Patel AP, Shahid M, Oksuz O, Rabkin SD, Martuza RL, Rivera MN, Louis DN, Kasif S, Chi AS, Bernstein BE (2013) An aberrant transcription factor network essential for Wnt signaling and stem cell maintenance in glioblastoma. Cell Rep 3(5):1567–1579. doi:10.1016/j.celrep.2013.04.021 Roese-Koerner B, Stappert L, Berger T, Braun NC, Veltel M, Jungverdorben J, Evert BO, Peitz M, Borghese L, Brustle O (2016) Reciprocal regulation between Bifunctional miR-9/9(*) and its transcriptional modulator Notch in human neural stem cell self-renewal and differentiation. Stem Cell Rep 7(2):207–219. doi:10.1016/j.stemcr.2016.06.008 Roncarati R, Sestan N, Scheinfeld MH, Berechid BE, Lopez PA, Meucci O, McGlade JC, Rakic P, D’Adamio L (2002) The gamma-secretase-generated intracellular domain of beta-amyloid precursor protein binds numb and inhibits Notch signaling. Proc Natl Acad Sci U S A 99(10):7102–7107. doi:10.1073/pnas.102192599 Ross SE, Greenberg ME, Stiles CD (2003) Basic helix-loop-helix factors in cortical development. Neuron 39(1):13–25 Saura CA, Choi SY, Beglopoulos V, Malkani S, Zhang D, Shankaranarayana Rao BS, Chattarji S, Kelleher RJ 3rd, Kandel ER, Duff K, Kirkwood A, Shen J (2004) Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration. Neuron 42(1):23–36 Schneider R, Grosschedl R (2007) Dynamics and interplay of nuclear architecture, genome organization, and gene expression. Genes Dev 21(23):3027–3043. doi:10.1101/gad.1604607 Schroeter EH, Kisslinger JA, Kopan R (1998) Notch-1 signalling requires ligand-induced proteolytic release of intracellular domain. Nature 393(6683):382–386. doi:10.1038/30756 Schuster-Gossler K, Cordes R, Muller J, Geffers I, Delany-Heiken P, Taft M, Preller M, Gossler A (2016) Context-dependent sensitivity to mutations disrupting the structural integrity of individual EGF repeats in the mouse Notch ligand DLL1. Genetics 202(3):1119–1133. doi:10.1534/genetics.115.184515 Sha L, Wu X, Yao Y, Wen B, Feng J, Sha Z, Wang X, Xing X, Dou W, Jin L, Li W, Wang N, Shen Y, Wang J, Wu L, Xu Q (2014) Notch signaling activation promotes seizure activity in temporal lobe epilepsy. Mol Neurobiol 49(2):633–644. doi:10.1007/s12035-013-8545-0 Sherrington R, Rogaev EI, Liang Y, Rogaeva EA, Levesque G, Ikeda M, Chi H, Lin C, Li G, Holman K, Tsuda T, Mar L, Foncin JF, Bruni AC, Montesi MP, Sorbi S, Rainero I, Pinessi L, Nee L, Chumakov I, Pollen D, Brookes A, Sanseau P, Polinsky RJ, Wasco W, Da Silva HA, Haines JL, Perkicak-Vance MA, Tanzi RE, Roses AD, Fraser PE, Rommens JM, St George-Hyslop PH (1995) Cloning of a gene bearing missense mutations in early-onset familial Alzheimer’s disease. Nature 375(6534):754–760. doi:10.1038/375754a0 Shetty AK, Hattiangady B, Shetty GA (2005) Stem/progenitor cell proliferation factors FGF-2, IGF-1, and VEGF exhibit early decline during the course of aging in the hippocampus: role of astrocytes. Glia 51(3):173–186. doi:10.1002/glia.20187 Shi Y, Zhao X, Hsieh J, Wichterle H, Impey S, Banerjee S, Neveu P, Kosik KS (2010) MicroRNA regulation of neural stem cells and neurogenesis. J Neurosci 30(45):14931–14936. doi:10.1523/JNEUROSCI.4280-10.2010 Shih AH, Holland EC (2006) Notch signaling enhances nestin expression in gliomas. Neoplasia 8(12):1072–1082. doi:10.1593/neo.06526 Shimada IS, Borders A, Aronshtam A, Spees JL (2011) Proliferating reactive astrocytes are regulated by Notch-1 in the peri-infarct area after stroke. Stroke 42(11):3231–3237. doi:10.1161/STROKEAHA.111.623280 Shimojo H, Ohtsuka T, Kageyama R (2008) Oscillations in notch signaling regulate maintenance of neural progenitors. Neuron 58(1):52–64. doi:10.1016/j.neuron.2008.02.014 Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, Henkelman RM, Cusimano MD, Dirks PB (2004) Identification of human brain tumour initiating cells. Nature 432(7015):396–401. doi:10.1038/nature03128 Song W, Nadeau P, Yuan M, Yang X, Shen J, Yankner BA (1999) Proteolytic release and nuclear translocation of Notch-1 are induced by presenilin-1 and impaired by pathogenic presenilin-1 mutations. Proc Natl Acad Sci U S A 96(12):6959–6963 Song Y, Lu B (2012) Interaction of Notch signaling modulator numb with alpha-Adaptin regulates endocytosis of Notch pathway components and cell fate determination of neural stem cells. J Biol Chem 287(21):17716–17728. doi:10.1074/jbc.M112.360719 Song Y, Willer JR, Scherer PC, Panzer JA, Kugath A, Skordalakes E, Gregg RG, Willer GB, Balice-Gordon RJ (2010) Neural and synaptic defects in slytherin, a zebrafish model for human congenital disorders of glycosylation. PLoS ONE 5(10):e13743. doi:10.1371/journal.pone.0013743 Stahl M, Uemura K, Ge C, Shi S, Tashima Y, Stanley P (2008) Roles of Pofut1 and O-fucose in mammalian Notch signaling. J Biol Chem 283(20):13638–13651. doi:10.1074/jbc.M802027200 Stump G, Durrer A, Klein AL, Lutolf S, Suter U, Taylor V (2002) Notch1 and its ligands Delta-like and Jagged are expressed and active in distinct cell populations in the postnatal mouse brain. Mech Dev 114(1–2):153–159 Suzuki H, Aoki K, Chiba K, Sato Y, Shiozawa Y, Shiraishi Y, Shimamura T, Niida A, Motomura K, Ohka F, Yamamoto T, Tanahashi K, Ranjit M, Wakabayashi T, Yoshizato T, Kataoka K, Yoshida K, Nagata Y, Sato-Otsubo A, Tanaka H, Sanada M, Kondo Y, Nakamura H, Mizoguchi M, Abe T, Muragaki Y, Watanabe R, Ito I, Miyano S, Natsume A, Ogawa S (2015) Mutational landscape and clonal architecture in grade II and III gliomas. Nat Genet 47(5):458–468. doi:10.1038/ng.3273 Szulwach KE, Li X, Smrt RD, Li Y, Luo Y, Lin L, Santistevan NJ, Li W, Zhao X, Jin P (2010) Cross talk between microRNA and epigenetic regulation in adult neurogenesis. J Cell Biol 189(1):127–141. doi:10.1083/jcb.200908151 Tiberi L, van den Ameele J, Dimidschstein J, Piccirilli J, Gall D, Herpoel A, Bilheu A, Bonnefont J, Iacovino M, Kyba M, Bouschet T, Vanderhaeghen P (2012) BCL6 controls neurogenesis through Sirt1-dependent epigenetic repression of selective Notch targets. Nat Neurosci 15(12):1627–1635. doi:10.1038/nn.3264 van Praag H, Kempermann G, Gage FH (1999) Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 2(3):266–270. doi:10.1038/6368 Wallberg AE, Pedersen K, Lendahl U, Roeder RG (2002) p300 and PCAF act cooperatively to mediate transcriptional activation from chromatin templates by notch intracellular domains in vitro. Mol Cell Biol 22(22):7812–7819 Wang J, Scully K, Zhu X, Cai L, Zhang J, Prefontaine GG, Krones A, Ohgi KA, Zhu P, Garcia-Bassets I, Liu F, Taylor H, Lozach J, Jayes FL, Korach KS, Glass CK, Fu XD, Rosenfeld MG (2007) Opposing LSD1 complexes function in developmental gene activation and repression programmes. Nature 446(7138):882–887. doi:10.1038/nature05671 Wang L, Chopp M, Zhang RL, Zhang L, Letourneau Y, Feng YF, Jiang A, Morris DC, Zhang ZG (2009a) The Notch pathway mediates expansion of a progenitor pool and neuronal differentiation in adult neural progenitor cells after stroke. Neuroscience 158(4):1356–1363. doi:10.1016/j.neuroscience.2008.10.064 Wang X, Mao X, Xie L, Greenberg DA, Jin K (2009b) Involvement of Notch1 signaling in neurogenesis in the subventricular zone of normal and ischemic rat brain in vivo. J Cereb Blood Flow Metab: Off J Int Soc Cereb Blood Flow Metab 29(10):1644–1654. doi:10.1038/jcbfm.2009.83 Webb AE, Pollina EA, Vierbuchen T, Urban N, Ucar D, Leeman DS, Martynoga B, Sewak M, Rando TA, Guillemot F, Wernig M, Brunet A (2013) FOXO3 shares common targets with ASCL1 genome-wide and inhibits ASCL1-dependent neurogenesis. Cell Rep 4(3):477–491. doi:10.1016/j.celrep.2013.06.035 Weng AP, Ferrando AA, Lee W, Morris JP, Silverman LB, Sanchez-Irizarry C, Blacklow SC, Look AT, Aster JC (2004) Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science 306(5694):269–271. doi:10.1126/science.1102160 Wu H, Coskun V, Tao J, Xie W, Ge W, Yoshikawa K, Li E, Zhang Y, Sun YE (2010) Dnmt3a-dependent nonpromoter DNA methylation facilitates transcription of neurogenic genes. Science 329(5990):444–448. doi:10.1126/science.1190485 Xu P, Qiu M, Zhang Z, Kang C, Jiang R, Jia Z, Wang G, Jiang H, Pu P (2010) The oncogenic roles of Notch1 in astrocytic gliomas in vitro and in vivo. J Neuro-Oncol 97(1):41–51. doi:10.1007/s11060-009-0007-1 Yagi H, Saito T, Yanagisawa M, Yu RK, Kato K (2012) Lewis X-carrying N-glycans regulate the proliferation of mouse embryonic neural stem cells via the Notch signaling pathway. J Biol Chem 287(29):24356–24364. doi:10.1074/jbc.M112.365643 Yamaguchi M, Tonou-Fujimori N, Komori A, Maeda R, Nojima Y, Li H, Okamoto H, Masai I (2005) Histone deacetylase 1 regulates retinal neurogenesis in zebrafish by suppressing Wnt and Notch signaling pathways. Development 132(13):3027–3043. doi:10.1242/dev.01881 Yousef H, Morgenthaler A, Schlesinger C, Bugaj L, Conboy IM, Schaffer DV (2015) Age-associated increase in BMP signaling inhibits hippocampal neurogenesis. Stem Cells 33(5):1577–1588. doi:10.1002/stem.1943 Zechner D, Fujita Y, Hulsken J, Muller T, Walther I, Taketo MM, Crenshaw EB 3rd, Birchmeier W, Birchmeier C (2003) Beta-catenin signals regulate cell growth and the balance between progenitor cell expansion and differentiation in the nervous system. Dev Biol 258(2):406–418 Zhang Z, Gao F, Kang X, Li J, Zhang L, Dong W, Jin Z, Li F, Gao N, Cai X, Yang S, Zhang J, Ren X, Yang X (2015) Exploring the potential relationship between Notch pathway genes expression and their promoter methylation in mice hippocampal neurogenesis. Brain Res Bull 113:8–16. doi:10.1016/j.brainresbull.2015.02.003 Zhao X, Ueba T, Christie BR, Barkho B, McConnell MJ, Nakashima K, Lein ES, Eadie BD, Willhoite AR, Muotri AR, Summers RG, Chun J, Lee KF, Gage FH (2003) Mice lacking methyl-CpG binding protein 1 have deficits in adult neurogenesis and hippocampal function. Proc Natl Acad Sci U S A 100(11):6777–6782. doi:10.1073/pnas.1131928100 Zhu TS, Costello MA, Talsma CE, Flack CG, Crowley JG, Hamm LL, He X, Hervey-Jumper SL, Heth JA, Muraszko KM, DiMeco F, Vescovi AL, Fan X (2011) Endothelial cells create a stem cell niche in glioblastoma by providing NOTCH ligands that nurture self-renewal of cancer stem-like cells. Cancer Res 71(18):6061–6072. doi:10.1158/0008-5472.CAN-10-4269