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Frontiers in Biology

Front. Biol.    2016, Vol. 11 Issue (3) : 151-167     DOI: 10.1007/s11515-016-1405-3
Transgenic mouse models for studying adult neurogenesis
Fatih Semerci1,2,Mirjana Maletic-Savatic1,2,3,*()
1. Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030, USA
2. Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, Houston, TX 77030, USA
3. Department of Pediatrics-Neurology, Department of Neuroscience, and Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, TX 77030, USA
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The mammalian hippocampus shows a remarkable capacity for continued neurogenesis throughout life. Newborn neurons, generated by the radial neural stem cells (NSCs), are important for learning and memory as well as mood control. During aging, the number and responses of NSCs to neurogenic stimuli diminish, leading to decreased neurogenesis and age-associated cognitive decline and psychiatric disorders. Thus, adult hippocampal neurogenesis has garnered significant interest because targeting it could be a novel potential therapeutic strategy for these disorders. However, if we are to use neurogenesis to halt or reverse hippocampal-related pathology, we need to understand better the core molecular machinery that governs NSC and their progeny. In this review, we summarize a wide variety of mouse models used in adult neurogenesis field, present their advantages and disadvantages based on specificity and efficiency of labeling of different cell types, and review their contribution to our understanding of the biology and the heterogeneity of different cell types found in adult neurogenic niches.

Keywords adult neurogenesis      mouse models      neural stem cells      neuroprogenitors      lineage tracing     
Corresponding Authors: Mirjana Maletic-Savatic   
Just Accepted Date: 25 May 2016   Online First Date: 23 June 2016    Issue Date: 05 July 2016
 Cite this article:   
Fatih Semerci,Mirjana Maletic-Savatic. Transgenic mouse models for studying adult neurogenesis[J]. Front. Biol., 2016, 11(3): 151-167.
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Fatih Semerci
Mirjana Maletic-Savatic
Fig.1  Summary of immunohistochemical markers, reporter and lineage tracing mouse models used to identify different cell types of the adult hippocampal neurogenic niche. NSC, neural stem cells; RGL, radial glia like cells; ANP, amplifying neuroprogenitors; IPC, intermediate progenitor cells. Upper part: Markers, Middle part: Reporter lines; Lower part: Lineage tracing lines. * denotes the mouse models that target mostly quiescent neural stem cells.
Fig.2  Summary of immunohistochemical markers, reporter and lineage tracing mouse models used to identify different cell types of the adult subventricular zone neurogenic niche. Broken strip (EGFR) indicates expression in only subset of Type B cells. EGFR+ population is actively cycling whereas EGFR population consists of quiescent SVZ neural stem cells. SVZ= subventricular zone; RMS= rostral migratory stream; OB= olfactory bulb. Upper part: Markers, Middle part: Reporter lines; Lower part: Lineage tracing lines.
Line Use Reference
Nestin Nestin::lacZ Characterization of regulatory regions of Nestin Zimmerman et al., 1994; Johansson et al., 2002
Nestin::CFPnuc Quantification of NSCs and progenitor cells Encinas et al., 2006
Nestin::GFP, Nestin::eGFP Population studies of NSCs and progenitor cells Yamaguchi et al., 2000; Kawaguchi et al., 2001; Mignone et al., 2004
Nestin::tTA, Nestin-rtTA, Nestin-rtTA-M2-eGFPNestin-Cre, Nestin-CreER; Nestin-CreERT2 Lineage tracing Mitsuhashi et al., 2001; Beech et al., 2004; Yu et al., 2005Betz et al., 1996; Kuo et al., 2006; Imayoshi et al., 2006; Lagace et al., 2007; Dranovsky et al., 2011
GFAP GFAP::GFP, GFAP::eGFP GFAP::AmCyan1, AsRed2, mRFP1 Population studies of astrocytes and NSCs Zhuo et al., 1997; Nolte et al., 2001; Hirrlinger et al., 2005; Platel et al., 2009
GFAP::TK Specific ablation of NSCs Garcia et al., 2004
GFAP-Cre, GFAP-CreERT2 Lineage tracing of NSCs Marino et al., 2000; Casper and McCarthy, 2006; Ganat et al., 2006
Sox1 Sox1-GFP Population studies of a subset of NSCs and ANPs Aubert et al., 2003
Sox1-tTA;tetO-Cre Lineage tracing of NSCs and ANPs Venere et al., 2012
Sox2 Sox2β-Geo Strong activity in SVZ but weak in SGZ Zappone et al., 2000
Sox2::GFP, Sox2-eGFP Population studies of NSCs, ANPs, and astrocytes D'Amour and Gage, 2003; Ellis et al., 2004
Sox2::Cre, Sox2::CreER, Sox2::CreERT2 Lineage tracing Hayashi et al., 2007; Favaro et al., 2009; Kang and Hebert, 2012
Ascl1 Ascl1-GFPnuc Strong expression in ANPs but weak in NSCs Leung et al., 2007
Ascl1-CreERT2 Lineage tracing in SGZ Kim et al., 2011
Glast Glast::eGFP Glast::dsRed Population studies of astrocytes and NSCs Gong et al., 2003 Glowatzki et al., 2006; Regan et al., 2007
Glast-CreERT2; Glast::CreERT2 Lineage tracing Mori et al., 2006; Slezak et al., 2007
Blbp Blbp::GFP, BLBP::eGFPBlbp::eYFP, Blbp::dsRed2Blbp::mCherry Population studies of astrocytes and NSCs Gong et al., 2003;Anthony et al., 2004; Schmid et al., 2006; Giachino et al., 2014
Blbp::Cre Lineage tracing Anthony et al., 2004; Hegedus et al., 2007
Hes5 Hes5::GFP Population studies of a subset of NSCs and ANPs Basak and Taylor, 2007
Hes5::CreERT2 Lineage tracing Lugert et al., 2012
Tbr2 EOMES::GFP Labeling of late ANPs and early NBs Kwon and Hadjantonakis, 2007
Tbr2::GFP Labeling of late ANPs, NBs, INs and some GCs Gong et al., 2003
EOMES-CreERT2Tbr2::CreERT2 Lineage tracing of late ANPs and NBs Pimeisl et al., 2013 Berg et al., 2015
Spot14 Spot14::GFP Labeling of subset of NSCs and ANPs Knobloch et al., 2013; Knobloch et al., 2014
Spot14::CreERT2 Lineage tracing Knobloch et al., 2013
Gli1 Gli1::CreERT2 Lineage tracing of NSCs in SGZ Ahn and Joyner, 2004
Prss56 Prss56-CreERT2 Lineage tracing of NSCs in SGZ Jourdon et al., 2015
Hopx Hopx-3FlagGFP/+ Labeling of NSCs of SGZ Li et al., 2015
Hopx-ERCre/+ Lineage tracing of NSCs in SGZ Li et al., 2015
Tctex-1 Tctex-1::GFP, Tctex-1::DsRed Labeling of NSCs, ANPs and NBs of SGZ Tseng et al., 2010
Pomc Pomc::eGFP Labeling of NBs/INs Cowley et al., 2001
Pomc-Cre Lineage tracing of NBs/INs Balthasar et al., 2004
Dcx Dcx-eGFP Dcx-DsRed Labeling of NBs/INs Labeling of NBs/INs Couillard-Despres et al., 2006; Walker et al., 2007 Couillard-Despres et al., 2006; Wang et al., 2007
Tab.1  List of reporter mice used in adult neurogenesis research.
1a Abiega O, Beccari S, Diaz-Aparicio I, Nadjar A, Layé S, Leyrolle Q, Gómez-Nicola D, Domercq M, Pérez-Samartín A, Sánchez-Zafra V, Paris I, Valero J, Savage JC, Hui CW, Tremblay MÈ, Deudero JJ, Brewster AL, Anderson AE, Zaldumbide L, Galbarriatu L, Marinas A, Vivanco M D, Matute C, Maletic-Savatic M, Encinas JM, Sierra A (2016). Neuronal hyperactivity disturbs ATP microgradients, impairs microglial motility, and reduces phagocytic receptor expression triggering apoptosis/microglial phagocytosis uncoupling. PLoS Biol, 14(5): e1002466
doi: 10.1186/1477-5956-11-18 pmid: 23621913
1 Abraham A B, Bronstein R, Chen E I, Koller A, Ronfani L, Maletic-Savatic M, Tsirka S E (2013a). Members of the high mobility group B protein family are dynamically expressed in embryonic neural stem cells. Proteome Sci, 11(1): 18
doi: 10.1186/1477-5956-11-18 pmid: 23621913
2 Abraham A B, Bronstein R, Reddy A S, Maletic-Savatic M, Aguirre A, Tsirka S E (2013b). Aberrant neural stem cell proliferation and increased adult neurogenesis in mice lacking chromatin protein HMGB2. PLoS ONE, 8(12): e84838
doi: 10.1371/journal.pone.0084838 pmid: 24391977
3 Ahn S, Joyner A L (2004). Dynamic changes in the response of cells to positive hedgehog signaling during mouse limb patterning. Cell, 118(4): 505–516
doi: 10.1016/j.cell.2004.07.023 pmid: 15315762
4 Ahn S, Joyner A L (2005). In vivo analysis of quiescent adult neural stem cells responding to Sonic hedgehog. Nature, 437(7060): 894–897
doi: 10.1038/nature03994 pmid: 16208373
5 Aimone J B, Deng W, Gage F H (2011). Resolving new memories: a critical look at the dentate gyrus, adult neurogenesis, and pattern separation. Neuron, 70(4): 589–596
doi: 10.1016/j.neuron.2011.05.010 pmid: 21609818
6 Akazawa C, Sasai Y, Nakanishi S, Kageyama R (1992). Molecular characterization of a rat negative regulator with a basic helix-loop-helix structure predominantly expressed in the developing nervous system. J Biol Chem, 267(30): 21879–21885
pmid: 1400497
7 Allen G I, Maletić-Savatić M (2011). Sparse non-negative generalized PCA with applications to metabolomics. Bioinformatics, 27(21): 3029–3035
doi: 10.1093/bioinformatics/btr522 pmid: 21930672
8 Allen G I, Peterson C, Vannucci M, Maletić-Savatić M (2013). Regularized partial least squares with an application to NMR spectroscopy. Stat Anal Data Min, 6(4): 302–314
doi: 10.1002/sam.11169 pmid: 24511361
9 Altman J (1962). Are new neurons formed in the brains of adult mammals? Science, 135(3509): 1127–1128
doi: 10.1126/science.135.3509.1127 pmid: 13860748
10 Alunni A, Krecsmarik M, Bosco A, Galant S, Pan L, Moens C B, Bally-Cuif L (2013). Notch3 signaling gates cell cycle entry and limits neural stem cell amplification in the adult pallium. Development, 140(16): 3335–3347
doi: 10.1242/dev.095018 pmid: 23863484
11 Alvarez-Buylla A, Kohwi M, Nguyen T M, Merkle F T (2008). The heterogeneity of adult neural stem cells and the emerging complexity of their niche. Cold Spring Harb Symp Quant Biol, 73(0): 357–365
doi: 10.1101/sqb.2008.73.019 pmid: 19022766
12 Andersson E R, Sandberg R, Lendahl U (2011). Notch signaling: simplicity in design, versatility in function. Development, 138(17): 3593–3612
doi: 10.1242/dev.063610 pmid: 21828089
13 Anthony T E, Klein C, Fishell G, Heintz N (2004). Radial glia serve as neuronal progenitors in all regions of the central nervous system. Neuron, 41(6): 881–890
doi: 10.1016/S0896-6273(04)00140-0 pmid: 15046721
14 Arnold J M, Choi W T, Sreekumar A, Maletić-Savatić M (2015). Analytical strategies for studying stem cell metabolism. Front Biol (Beijing), 10(2): 141–153
doi: 10.1007/s11515-015-1357-z pmid: 26213533
15 Arnold K, Sarkar A, Yram M A, Polo J M, Bronson R, Sengupta S, Seandel M, Geijsen N, Hochedlinger K (2011). Sox2(+) adult stem and progenitor cells are important for tissue regeneration and survival of mice. Cell Stem Cell, 9(4): 317–329
doi: 10.1016/j.stem.2011.09.001 pmid: 21982232
16 Aubert J, Stavridis M P, Tweedie S, O’Reilly M, Vierlinger K, Li M, Ghazal P, Pratt T, Mason J O, Roy D, Smith A (2003). Screening for mammalian neural genes via fluorescence-activated cell sorter purification of neural precursors from Sox1-gfp knock-in mice. Proc Natl Acad Sci USA, 100(Suppl 1): 11836–11841
doi: 10.1073/pnas.1734197100 pmid: 12923295
17 Balordi F, Fishell G (2007). Mosaic removal of hedgehog signaling in the adult SVZ reveals that the residual wild-type stem cells have a limited capacity for self-renewal. J Neurosci, 27(52): 14248–14259
doi: 10.1523/JNEUROSCI.4531-07.2007 pmid: 18160632
18 Balthasar N, Coppari R, McMinn J, Liu S M, Lee C E, Tang V, Kenny C D, McGovern R A, Chua S C Jr, Elmquist J K, Lowell B B (2004). Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis. Neuron, 42(6): 983–991
doi: 10.1016/j.neuron.2004.06.004 pmid: 15207242
19 Basak O, Giachino C, Fiorini E, Macdonald H R, 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 pmid: 22514327
20 Basak O, Taylor V (2007). Identification of self-replicating multipotent progenitors in the embryonic nervous system by high Notch activity and Hes5 expression. Eur J Neurosci, 25(4): 1006–1022
doi: 10.1111/j.1460-9568.2007.05370.x pmid: 17331197
21 Beckervordersandforth R, Deshpande A, Schäffner I, Huttner H B, Lepier A, Lie D C, Götz M (2014). In vivo targeting of adult neural stem cells in the dentate gyrus by a split-cre approach. Stem Cell Rep, 2(2): 153–162
doi: 10.1016/j.stemcr.2014.01.004 pmid: 24527389
22 Beech R D, Cleary M A, Treloar H B, Eisch A J, Harrist A V, Zhong W, Greer C A, Duman R S, Picciotto M R (2004). Nestin promoter/enhancer directs transgene expression to precursors of adult generated periglomerular neurons. J Comp Neurol, 475(1): 128–141
doi: 10.1002/cne.20179 pmid: 15176089
23 Berg D A, Yoon K J, Will B, Xiao A Y, Kim N S, Christian K M, Song H, Ming G (2015). Tbr2-expressing intermediate progenitor cells in the adult mouse hippocampus are unipotent neuronal precursors with limited amplification capacity under homeostasis. Frontiers in Biology, 10(3): 262–271
doi: 10.1007/s11515-015-1364-0
24 Berninger B, Costa M R, Koch U, Schroeder T, Sutor B, Grothe B, Götz M (2007). Functional properties of neurons derived from in vitro reprogrammed postnatal astroglia. J Neurosci, 27(32): 8654–8664
doi: 10.1523/JNEUROSCI.1615-07.2007 pmid: 17687043
25 Bertrand N, Castro D S, Guillemot F (2002). Proneural genes and the specification of neural cell types. Nat Rev Neurosci, 3(7): 517–530
doi: 10.1038/nrn874 pmid: 12094208
26 Betz U A, Vosshenrich C A, Rajewsky K, Müller W (1996). Bypass of lethality with mosaic mice generated by Cre-loxP-mediated recombination. Curr Biol, 6(10): 1307–1316
doi: 10.1016/S0960-9822(02)70717-3 pmid: 8939573
27 Bonaguidi M A, Song J, Ming G L, Song H (2012). A unifying hypothesis on mammalian neural stem cell properties in the adult hippocampus. Curr Opin Neurobiol, 22(5): 754–761
doi: 10.1016/j.conb.2012.03.013 pmid: 22503352
28 Bonaguidi M A, Wheeler M A, Shapiro J S, Stadel R P, Sun G J, Ming G L, Song H (2011). In vivo clonal analysis reveals self-renewing and multipotent adult neural stem cell characteristics. Cell, 145(7): 1142–1155
doi: 10.1016/j.cell.2011.05.024 pmid: 21664664
29 Bond A M, Ming G L, Song H (2015). Adult mammalian neural stem cells and neurogenesis: Five Decades Later. Cell Stem Cell, 17(4): 385–395
doi: 10.1016/j.stem.2015.09.003 pmid: 26431181
30 Bracko O, Singer T, Aigner S, Knobloch M, Winner B, Ray J, Clemenson G D Jr, Suh H, Couillard-Despres S, Aigner L, Gage F H, Jessberger S (2012). Gene expression profiling of neural stem cells and their neuronal progeny reveals IGF2 as a regulator of adult hippocampal neurogenesis. J Neurosci, 32(10): 3376–3387
doi: 10.1523/JNEUROSCI.4248-11.2012 pmid: 22399759
31 Breunig J J, Silbereis J, Vaccarino F M, Sestan N, Rakic P (2007). Notch regulates cell fate and dendrite morphology of newborn neurons in the postnatal dentate gyrus. Proc Natl Acad Sci USA, 104(51): 20558–20563
doi: 10.1073/pnas.0710156104 pmid: 18077357
32 Brill M S, Ninkovic J, Winpenny E, Hodge R D, Ozen I, Yang R, Lepier A, Gascón S, Erdelyi F, Szabo G, Parras C, Guillemot F, Frotscher M, Berninger B, Hevner R F, Raineteau O, Götz M (2009). Adult generation of glutamatergic olfactory bulb interneurons. Nat Neurosci, 12(12): 1524–1533
doi: 10.1038/nn.2416 pmid: 19881504
33 Cameron H A, Woolley C S, McEwen B S, Gould E (1993). Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat. Neuroscience, 56(2): 337–344
doi: 10.1016/0306-4522(93)90335-D pmid: 8247264
34 Casper K B, McCarthy K D (2006). GFAP-positive progenitor cells produce neurons and oligodendrocytes throughout the CNS. Mol Cell Neurosci, 31(4): 676–684
doi: 10.1016/j.mcn.2005.12.006 pmid: 16458536
35 Chapouton P, Skupien P, Hesl B, Coolen M, Moore J C, Madelaine R, Kremmer E, Faus-Kessler T, Blader P, Lawson N D, Bally-Cuif L (2010). Notch activity levels control the balance between quiescence and recruitment of adult neural stem cells. J Neurosci, 30(23): 7961–7974
doi: 10.1523/JNEUROSCI.6170-09.2010 pmid: 20534844
36 Chen J, Kelz M B, Zeng G, Sakai N, Steffen C, Shockett P E, Picciotto M R, Duman R S, Nestler E J (1998). Transgenic animals with inducible, targeted gene expression in brain. Mol Pharmacol, 54(3): 495–503
pmid: 9730908
37 Chojnacki A K, Mak G K, Weiss S (2009). Identity crisis for adult periventricular neural stem cells: subventricular zone astrocytes, ependymal cells or both? Nat Rev Neurosci, 10(2): 153–163
doi: 10.1038/nrn2571 pmid: 19153578
38 Chuang J Z, Milner T A, Sung C H (2001). Subunit heterogeneity of cytoplasmic dynein: Differential expression of 14 kDa dynein light chains in rat hippocampus. J Neurosci, 21(15): 5501–5512
pmid: 11466421
39 Clelland C D, Choi M, Romberg C, Clemenson G D Jr, Fragniere A, Tyers P, Jessberger S, Saksida L M, Barker R A, Gage F H, Bussey T J (2009). A functional role for adult hippocampal neurogenesis in spatial pattern separation. Science, 325(5937): 210–213
doi: 10.1126/science.1173215 pmid: 19590004
40 Codega P, Silva-Vargas V, Paul A, Maldonado-Soto A R, Deleo A M, Pastrana E, Doetsch F (2014). Prospective identification and purification of quiescent adult neural stem cells from their in vivo niche. Neuron, 82(3): 545–559
doi: 10.1016/j.neuron.2014.02.039 pmid: 24811379
41 Collignon J (1992). Study of a new family of genes related to the mammalian testis determining gene (Phd Thesis: CNAA London).
42 Couillard-Despres S, Winner B, Karl C, Lindemann G, Schmid P, Aigner R, Laemke J, Bogdahn U, Winkler J, Bischofberger J, Aigner L (2006). Targeted transgene expression in neuronal precursors: watching young neurons in the old brain. Eur J Neurosci, 24(6): 1535–1545
doi: 10.1111/j.1460-9568.2006.05039.x pmid: 17004917
43 Cowley M A, Smart J L, Rubinstein M, Cerdán M G, Diano S, Horvath T L, Cone R D, Low M J (2001). Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature, 411(6836): 480–484
doi: 10.1038/35078085 pmid: 11373681
44 D’Amour K A, Gage F H (2003). Genetic and functional differences between multipotent neural and pluripotent embryonic stem cells. Proc Natl Acad Sci USA, 100(Suppl 1): 11866–11872
doi: 10.1073/pnas.1834200100 pmid: 12923297
45 David D J, Wang J, Samuels B A, Rainer Q, David I, Gardier A M, Hen R (2010). Implications of the functional integration of adult-born hippocampal neurons in anxiety-depression disorders. Neuroscientist, 16(5): 578–591
doi: 10.1177/1073858409360281 pmid: 20889967
46 Day K, Shefer G, Richardson J B, Enikolopov G, Yablonka-Reuveni Z (2007). Nestin-GFP reporter expression defines the quiescent state of skeletal muscle satellite cells. Dev Biol, 304(1): 246–259
doi: 10.1016/j.ydbio.2006.12.026 pmid: 17239845
47 DeCarolis N A, Mechanic M, Petrik D, Carlton A, Ables J L, Malhotra S, Bachoo R, Götz M, Lagace D C, Eisch A J (2013). In vivo contribution of nestin- and GLAST-lineage cells to adult hippocampal neurogenesis. Hippocampus, 23(8): 708–719
doi: 10.1002/hipo.22130 pmid: 23554226
48 Dedesma C, Chuang J Z, Alfinito P D, Sung C H (2006). Dynein light chain Tctex-1 identifies neural progenitors in adult brain. J Comp Neurol, 496(6): 773–786
doi: 10.1002/cne.20958 pmid: 16628620
49 Deng W, Saxe M D, Gallina I S, Gage F H (2009). Adult-born hippocampal dentate granule cells undergoing maturation modulate learning and memory in the brain. J Neurosci, 29(43): 13532–13542
doi: 10.1523/JNEUROSCI.3362-09.2009 pmid: 19864566
50 Djuric P M, Wagshul M E, Henn F B,  Enikolopov G, Maletic-Savatic M ( (2008). Singular Value Decomposition algorithm for detection of neural progenitor cells in the live human brain. Science, 321: 640
doi: 10.1126/science.1156889 pmid: 26380846
51 Doetsch F, García-Verdugo J M, Alvarez-Buylla A (1997). Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain. J Neurosci, 17(13): 5046–5061
pmid: 9185542
52 Doetsch F, García-Verdugo J M, Alvarez-Buylla A (1999). Regeneration of a germinal layer in the adult mammalian brain. Proc Natl Acad Sci USA, 96(20): 11619–11624
doi: 10.1073/pnas.96.20.11619 pmid: 10500226
53 Dranovsky A, Picchini A M, Moadel T, Sisti A C, Yamada A, Kimura S, Leonardo E D, Hen R (2011). Experience dictates stem cell fate in the adult hippocampus. Neuron, 70(5): 908–923
doi: 10.1016/j.neuron.2011.05.022 pmid: 21658584
54 Dupret D, Revest J M, Koehl M, Ichas F, De Giorgi F, Costet P, Abrous D N, Piazza P V (2008). Spatial relational memory requires hippocampal adult neurogenesis. PLoS One, 3: e1959
55 Ellis P, Fagan B M, Magness S T, Hutton S, Taranova O, Hayashi S, McMahon A, Rao M, Pevny L (2004). SOX2, a persistent marker for multipotential neural stem cells derived from embryonic stem cells, the embryo or the adult. Dev Neurosci, 26(2-4): 148–165
doi: 10.1159/000082134 pmid: 15711057
56 Encinas J M, Michurina T V, Peunova N, Park J H, Tordo J, Peterson D A, Fishell G, Koulakov A, Enikolopov G (2011). Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippocampus. Cell Stem Cell, 8(5): 566–579
doi: 10.1016/j.stem.2011.03.010 pmid: 21549330
57 Encinas J M, Vaahtokari A, Enikolopov G (2006). Fluoxetine targets early progenitor cells in the adult brain. Proc Natl Acad Sci USA, 103(21): 8233–8238
doi: 10.1073/pnas.0601992103 pmid: 16702546
58 Englund C, Fink A, Lau C, Pham D, Daza R A, Bulfone A, Kowalczyk T, Hevner R F (2005). Pax6, Tbr2, and Tbr1 are expressed sequentially by radial glia, intermediate progenitor cells, and postmitotic neurons in developing neocortex. J Neurosci, 25(1): 247–251
doi: 10.1523/JNEUROSCI.2899-04.2005 pmid: 15634788
59 Eriksson P S, Perfilieva E, Björk-Eriksson T, Alborn A M, Nordborg C, Peterson D A, Gage F H (1998). Neurogenesis in the adult human hippocampus. Nat Med, 4(11): 1313–1317
doi: 10.1038/3305 pmid: 9809557
60 Farioli-Vecchioli S, Saraulli D, Costanzi M, Pacioni S, Cinà I, Aceti M, Micheli L, Bacci A, Cestari V, Tirone F (2008). The timing of differentiation of adult hippocampal neurons is crucial for spatial memory. PLoS Biol, 6(10): e246
doi: 10.1371/journal.pbio.0060246 pmid: 18842068
61 Farnsworth D R, Bayraktar O A, Doe C Q (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 pmid: 26585279
62 Favaro R, Valotta M, Ferri A L, Latorre E, Mariani J, Giachino C, Lancini C, Tosetti V, Ottolenghi S, Taylor V, Nicolis S K (2009). Hippocampal development and neural stem cell maintenance require Sox2-dependent regulation of Shh. Nat Neurosci, 12(10): 1248–1256
doi: 10.1038/nn.2397 pmid: 19734891
63 Ferri A L, Cavallaro M, Braida D, Di Cristofano A, Canta A, Vezzani A, Ottolenghi S, Pandolfi P P, Sala M, DeBiasi S, Nicolis S K (2004). Sox2 deficiency causes neurodegeneration and impaired neurogenesis in the adult mouse brain. Development, 131(15): 3805–3819
doi: 10.1242/dev.01204 pmid: 15240551
64 Filippov V, Kronenberg G, Pivneva T, Reuter K, Steiner B, Wang L P, Yamaguchi M, Kettenmann H, Kempermann G (2003). Subpopulation of nestin-expressing progenitor cells in the adult murine hippocampus shows electrophysiological and morphological characteristics of astrocytes. Mol Cell Neurosci, 23(3): 373–382
doi: 10.1016/S1044-7431(03)00060-5 pmid: 12837622
65 Gama-Norton L, Ferrando E, Ruiz-Herguido C, Liu Z, Guiu J, Islam A B, Lee S U, Yan M, Guidos C J, López-Bigas N, Maeda T, Espinosa L, Kopan R, Bigas A (2015). Notch signal strength controls cell fate in the haemogenic endothelium. Nat Commun, 6: 8510
doi: 10.1038/ncomms9510 pmid: 26465397
66 Ganat Y M, Silbereis J, Cave C, Ngu H, Anderson G M, Ohkubo Y, Ment L R, Vaccarino F M (2006). Early postnatal astroglial cells produce multilineage precursors and neural stem cells in vivo. J Neurosci, 26(33): 8609–8621
doi: 10.1523/JNEUROSCI.2532-06.2006 pmid: 16914687
67 Garcia A D, Doan N B, Imura T, Bush T G, Sofroniew M V (2004). GFAP-expressing progenitors are the principal source of constitutive neurogenesis in adult mouse forebrain. Nat Neurosci, 7(11): 1233–1241
doi: 10.1038/nn1340 pmid: 15494728
68 Gheusi G, Cremer H, McLean H, Chazal G, Vincent J D, Lledo P M (2000). Importance of newly generated neurons in the adult olfactory bulb for odor discrimination. Proc Natl Acad Sci USA, 97(4): 1823–1828
doi: 10.1073/pnas.97.4.1823 pmid: 10677540
69 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 pmid: 23964022
70 Giachino C, Taylor V (2014). Notching up neural stem cell homogeneity in homeostasis and disease. Front Neurosci, 8: 32
doi: 10.3389/fnins.2014.00032 pmid: 24611040
71 Glowatzki E, Cheng N, Hiel H, Yi E, Tanaka K, Ellis-Davies G C, Rothstein J D, Bergles D E (2006). The glutamate-aspartate transporter GLAST mediates glutamate uptake at inner hair cell afferent synapses in the mammalian cochlea. J Neurosci, 26(29): 7659–7664
doi: 10.1523/JNEUROSCI.1545-06.2006 pmid: 16855093
72 Gong S, Zheng C, Doughty M L, Losos K, Didkovsky N, Schambra U B, Nowak N J, Joyner A, Leblanc G, Hatten M E, Heintz N (2003). A gene expression atlas of the central nervous system based on bacterial artificial chromosomes. Nature, 425(6961): 917–925
doi: 10.1038/nature02033 pmid: 14586460
73 Hartfuss E, Galli R, Heins N, Götz M (2001). Characterization of CNS precursor subtypes and radial glia. Dev Biol, 229(1): 15–30
doi: 10.1006/dbio.2000.9962 pmid: 11133151
74 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 pmid: 15496443
75 Hayashi A, Koob J W, Liu D Z, Tong A Y, Hunter D A, Parsadanian A, Mackinnon S E, Myckatyn T M (2007). A double-transgenic mouse used to track migrating Schwann cells and regenerating axons following engraftment of injured nerves. Exp Neurol, 207(1): 128–138
doi: 10.1016/j.expneurol.2007.06.004 pmid: 17628544
76 Hegedus B, Dasgupta B, Shin J E, Emnett R J, Hart-Mahon E K, Elghazi L, Bernal-Mizrachi E, Gutmann D H (2007). Neurofibromatosis-1 regulates neuronal and glial cell differentiation from neuroglial progenitors in vivo by both cAMP- and Ras-dependent mechanisms. Cell Stem Cell, 1(4): 443–457
doi: 10.1016/j.stem.2007.07.008 pmid: 18371380
77 Heine V M, Zareno J, Maslam S, Joëls M, Lucassen P J (2005). Chronic stress in the adult dentate gyrus reduces cell proliferation near the vasculature and VEGF and Flk-1 protein expression. Eur J Neurosci, 21(5): 1304–1314
doi: 10.1111/j.1460-9568.2005.03951.x pmid: 15813940
78 Hirrlinger P G, Scheller A, Braun C, Quintela-Schneider M, Fuss B, Hirrlinger J, Kirchhoff F (2005). Expression of reef coral fluorescent proteins in the central nervous system of transgenic mice. Mol Cell Neurosci, 30(3): 291–303
doi: 10.1016/j.mcn.2005.08.011 pmid: 16169246
79 Hockfield S, McKay R D (1985). Identification of major cell classes in the developing mammalian nervous system. J Neurosci, 5(12): 3310–3328
pmid: 4078630
80 Hodge R D, Kowalczyk T D, Wolf S A, Encinas J M, Rippey C, Enikolopov G, Kempermann G, Hevner R F (2008). Intermediate progenitors in adult hippocampal neurogenesis: Tbr2 expression and coordinate regulation of neuronal output. J Neurosci, 28(14): 3707–3717
doi: 10.1523/JNEUROSCI.4280-07.2008 pmid: 18385329
81 Hunt R F, Dinday M T, Hindle-Katel W, Baraban S C (2012). LIS1 deficiency promotes dysfunctional synaptic integration of granule cells generated in the developing and adult dentate gyrus. J Neurosci, 32(37): 12862–12875
doi: 10.1523/JNEUROSCI.1286-12.2012 pmid: 22973010
82 Imayoshi I, Ohtsuka T, Metzger D, Chambon P, Kageyama R (2006). Temporal regulation of Cre recombinase activity in neural stem cells. Genesis, 44(5): 233–238
doi: 10.1002/dvg.20212 pmid: 16652364
83 Imayoshi I, Sakamoto M, Ohtsuka T, Takao K, Miyakawa T, Yamaguchi M, Mori K, Ikeda T, Itohara S, Kageyama R (2008). Roles of continuous neurogenesis in the structural and functional integrity of the adult forebrain. Nat Neurosci, 11(10): 1153–1161
doi: 10.1038/nn.2185 pmid: 18758458
84 Jacobs B L, van Praag H, Gage F H (2000). Adult brain neurogenesis and psychiatry: a novel theory of depression. Mol Psychiatry, 5(3): 262–269
doi: 10.1038/ pmid: 10889528
85 Jessberger S, Toni N, Clemenson G D Jr, Ray J, Gage F H (2008). Directed differentiation of hippocampal stem/progenitor cells in the adult brain. Nat Neurosci, 11(8): 888–893
doi: 10.1038/nn.2148 pmid: 18587391
86 Joëls M, Karst H, Krugers H J, Lucassen P J (2007). Chronic stress: implications for neuronal morphology, function and neurogenesis. Front Neuroendocrinol, 28(2-3): 72–96
doi: 10.1016/j.yfrne.2007.04.001 pmid: 17544065
87 Johansson C B, Lothian C, Molin M, Okano H, Lendahl U (2002). Nestin enhancer requirements for expression in normal and injured adult CNS. J Neurosci Res, 69(6): 784–794
doi: 10.1002/jnr.10376 pmid: 12205672
88 Josephson R, Müller T, Pickel J, Okabe S, Reynolds K, Turner P A, Zimmer A, McKay R D (1998). POU transcription factors control expression of CNS stem cell-specific genes. Development, 125(16): 3087–3100
pmid: 9671582
89 Jourdon A, Gresset A, Spassky N, Charnay P, Topilko P, Santos R (2015). Prss56, a novel marker of adult neurogenesis in the mouse brain. Brain Struct Funct, doi: 10.1007/s00429-015-1171-z
90 Jump D B, Oppenheimer J H (1985). High basal expression and 3,5,3′-triiodothyronine regulation of messenger ribonucleic acid S14 in lipogenic tissues. Endocrinology, 117(6): 2259–2266
doi: 10.1210/endo-117-6-2259 pmid: 4065033
91 Kageyama R, Ohtsuka T (1999). The Notch-Hes pathway in mammalian neural development. Cell Res, 9(3): 179–188
doi: 10.1038/ pmid: 10520600
92 Kamachi Y, Kondoh H (2013). Sox proteins: regulators of cell fate specification and differentiation. Development, 140(20): 4129–4144
doi: 10.1242/dev.091793 pmid: 24086078
93 Kang W, Hébert J M (2012). A Sox2 BAC transgenic approach for targeting adult neural stem cells. PLoS ONE, 7(11): e49038
doi: 10.1371/journal.pone.0049038 pmid: 23145058
94 Karow M, Sánchez R, Schichor C, Masserdotti G, Ortega F, Heinrich C, Gascón S, Khan M A, Lie D C, Dellavalle A, Cossu G, Goldbrunner R, Götz M, Berninger B (2012). Reprogramming of pericyte-derived cells of the adult human brain into induced neuronal cells. Cell Stem Cell, 11(4): 471–476
doi: 10.1016/j.stem.2012.07.007 pmid: 23040476
95 Kawaguchi A, Miyata T, Sawamoto K, Takashita N, Murayama A, Akamatsu W, Ogawa M, Okabe M, Tano Y, Goldman S A, Okano H (2001). Nestin-EGFP transgenic mice: visualization of the self-renewal and multipotency of CNS stem cells. Mol Cell Neurosci, 17(2): 259–273
doi: 10.1006/mcne.2000.0925 pmid: 11178865
96 Kim E J, Ables J L, Dickel L K, Eisch A J, Johnson J E (2011). Ascl1 (Mash1) defines cells with long-term neurogenic potential in subgranular and subventricular zones in adult mouse brain. PLoS ONE, 6(3): e18472
doi: 10.1371/journal.pone.0018472 pmid: 21483754
97 Kim E J, Leung C T, Reed R R, Johnson J E (2007). In vivo analysis of Ascl1 defined progenitors reveals distinct developmental dynamics during adult neurogenesis and gliogenesis. J Neurosci, 27(47): 12764–12774
doi: 10.1523/JNEUROSCI.3178-07.2007 pmid: 18032648
98 Kitamura T, Saitoh Y, Takashima N, Murayama A, Niibori Y, Ageta H, Sekiguchi M, Sugiyama H, Inokuchi K (2009). Adult neurogenesis modulates the hippocampus-dependent period of associative fear memory. Cell, 139(4): 814–827
doi: 10.1016/j.cell.2009.10.020 pmid: 19914173
99 Knobloch M, Braun S M, Zurkirchen L, von Schoultz C, Zamboni N, Araúzo-Bravo M J, Kovacs W J, Karalay O, Suter U, Machado R A, Roccio M, Lutolf M P, Semenkovich C F, Jessberger S (2013). Metabolic control of adult neural stem cell activity by Fasn-dependent lipogenesis. Nature, 493(7431): 226–230
doi: 10.1038/nature11689 pmid: 23201681
100 Knobloch M, von Schoultz C, Zurkirchen L, Braun S M, Vidmar M, Jessberger S (2014). SPOT14-positive neural stem/progenitor cells in the hippocampus respond dynamically to neurogenic regulators. Stem Cell Rep, 3(5): 735–742
doi: 10.1016/j.stemcr.2014.08.013 pmid: 25418721
101 Kuo C T, Mirzadeh Z, Soriano-Navarro M, Rasin M, Wang D, Shen J, Sestan N, Garcia-Verdugo J, Alvarez-Buylla A, Jan L Y, Jan Y N (2006). Postnatal deletion of Numb/Numblike reveals repair and remodeling capacity in the subventricular neurogenic niche. Cell, 127(6): 1253–1264
doi: 10.1016/j.cell.2006.10.041 pmid: 17174898
102 Kwon G S, Hadjantonakis A K (2007). Eomes: GFP-a tool for live imaging cells of the trophoblast, primitive streak, and telencephalon in the mouse embryo. Genesis, 45(4): 208–217
doi: 10.1002/dvg.20293 pmid: 17417802
103 Lagace D C, Whitman M C, Noonan M A, Ables J L, DeCarolis N A, Arguello A A, Donovan M H, Fischer S J, Farnbauch L A, Beech R D, DiLeone R J, Greer C A, Mandyam C D, Eisch A J (2007). Dynamic contribution of nestin-expressing stem cells to adult neurogenesis. J Neurosci, 27(46): 12623–12629
doi: 10.1523/JNEUROSCI.3812-07.2007 pmid: 18003841
104 Lai K, Kaspar B K, Gage F H, Schaffer D V (2003). Sonic hedgehog regulates adult neural progenitor proliferation in vitro and in vivo. Nat Neurosci, 6(1): 21–27
doi: 10.1038/nn983 pmid: 12469128
105 Lendahl U, Zimmerman L B, McKay R D (1990). CNS stem cells express a new class of intermediate filament protein. Cell, 60(4): 585–595
doi: 10.1016/0092-8674(90)90662-X pmid: 1689217
106 Leung C T, Coulombe P A, Reed R R (2007). Contribution of olfactory neural stem cells to tissue maintenance and regeneration. Nat Neurosci, 10(6): 720–726
doi: 10.1038/nn1882 pmid: 17468753
107 Li D, Takeda N, Jain R, Manderfield L J, Liu F, Li L, Anderson S A, Epstein J A (2015). Hopx distinguishes hippocampal from lateral ventricle neural stem cells. Stem Cell Res (Amst), 15(3): 522–529
doi: 10.1016/j.scr.2015.09.015 pmid: 26451648
108 Li L, Mignone J, Yang M, Matic M, Penman S, Enikolopov G, Hoffman R M (2003). Nestin expression in hair follicle sheath progenitor cells. Proc Natl Acad Sci USA, 100(17): 9958–9961
doi: 10.1073/pnas.1733025100 pmid: 12904579
109 Li X, Zhao X, Fang Y, Jiang X, Duong T, Fan C, Huang C C, Kain S R (1998). Generation of destabilized green fluorescent protein as a transcription reporter. J Biol Chem, 273(52): 34970–34975
doi: 10.1074/jbc.273.52.34970 pmid: 9857028
110 Lobo M V, Arenas M I, Alonso F J, Gomez G, Bazán E, Paíno C L, Fernández E, Fraile B, Paniagua R, Moyano A, Caso E (2004). Nestin, a neuroectodermal stem cell marker molecule, is expressed in Leydig cells of the human testis and in some specific cell types from human testicular tumours. Cell Tissue Res, 316(3): 369–376
doi: 10.1007/s00441-003-0848-4 pmid: 15127288
111 Lois C, Alvarez-Buylla A (1994). Long-distance neuronal migration in the adult mammalian brain. Science, 264(5162): 1145–1148
doi: 10.1126/science.8178174 pmid: 8178174
112 Lothian C, Prakash N, Lendahl U, Wahlström G M (1999). Identification of both general and region-specific embryonic CNS enhancer elements in the nestin promoter. Exp Cell Res, 248(2): 509–519
doi: 10.1006/excr.1999.4417 pmid: 10222142
113 Lucassen P J, Oomen C A, Naninck E F, Fitzsimons C P, van Dam A M, Czeh B, Korosi A (2015). Regulation of Adult Neurogenesis and Plasticity by (Early) Stress, Glucocorticoids, and Inflammation. Cold Spring Harb Perspect Biol, 7(9): a021303
doi: 10.1101/cshperspect.a021303 pmid: 26330520
114 Lugert S, Basak O, Knuckles P, Haussler U, Fabel K, Götz M, Haas C A, 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 pmid: 20452319
115 Lugert S, Vogt M, Tchorz J S, Müller M, Giachino C, Taylor V (2012). Homeostatic neurogenesis in the adult hippocampus does not involve amplification of Ascl1(high) intermediate progenitors. Nat Commun, 3: 670
doi: 10.1038/ncomms1670 pmid: 22334073
116 Luskin M B (1993). Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone. Neuron, 11(1): 173–189
doi: 10.1016/0896-6273(93)90281-U pmid: 8338665
117 Machold R, Hayashi S, Rutlin M, Muzumdar M D, Nery S, Corbin J G, Gritli-Linde A, Dellovade T, Porter J A, Rubin L L, Dudek H, McMahon A P, Fishell G (2003). Sonic hedgehog is required for progenitor cell maintenance in telencephalic stem cell niches. Neuron, 39(6): 937–950
doi: 10.1016/S0896-6273(03)00561-0 pmid: 12971894
118a Mainen Z F, Maletic-Savatic M, Shi S H, Hayashi Y, Malinow R, Svoboda K (1999). Two-photon imaging in living brain slices. Methods, 18: 231–239
doi: 10.1038/nn1928 pmid: 17603480
118 Mak G K, Enwere E K, Gregg C, Pakarainen T, Poutanen M, Huhtaniemi I, Weiss S (2007). Male pheromone-stimulated neurogenesis in the adult female brain: possible role in mating behavior. Nat Neurosci, 10(8): 1003–1011
doi: 10.1038/nn1928 pmid: 17603480
119 Malberg J E, Eisch A J, Nestler E J, Duman R S (2000). Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci, 20(24): 9104–9110
pmid: 11124987
120 Maletić-Savatić M, Vingara L K, Manganas L N, Li Y, Zhang S, Sierra A, Hazel R, Smith D, Wagshul M E, Henn F, Krupp L, Enikolopov G, Benveniste H, Djurić P M, Pelczer I (2008). Metabolomics of neural progenitor cells: a novel approach to biomarker discovery. Cold Spring Harb Symp Quant Biol, 73(0): 389–401
doi: 10.1101/sqb.2008.73.021 pmid: 19022759
121 Manganas L N, Maletic-Savatic M (2005). Stem cell therapy for central nervous system demyelinating disease. Curr Neurol Neurosci Rep, 5(3): 225–231
doi: 10.1007/s11910-005-0050-z pmid: 15865888
122 Manganas L N, Zhang X, Li Y, Hazel R D, Smith S D, Wagshul M E, Henn F, Benveniste H, Djuric P M, Enikolopov G, Maletic-Savatic M (2007). Magnetic resonance spectroscopy identifies neural progenitor cells in the live human brain. Science, 318(5852): 980–985
doi: 10.1126/science.1147851 pmid: 17991865
123 Marino S, Vooijs M, van Der Gulden H, Jonkers J, Berns A (2000). Induction of medulloblastomas in p53-null mutant mice by somatic inactivation of Rb in the external granular layer cells of the cerebellum. Genes Dev, 14(8): 994–1004
pmid: 10783170
124 Mayer E J, Hughes E H, Carter D A, Dick A D (2003). Nestin positive cells in adult human retina and in epiretinal membranes. Br J Ophthalmol, 87(9): 1154–1158
doi: 10.1136/bjo.87.9.1154 pmid: 12928287
125 McConnell J, Petrie L, Stennard F, Ryan K, Nichols J (2005). Eomesodermin is expressed in mouse oocytes and pre-implantation embryos. Mol Reprod Dev, 71(4): 399–404
doi: 10.1002/mrd.20318 pmid: 15880683
126 McHugh T J, Jones M W, Quinn J J, Balthasar N, Coppari R, Elmquist J K, Lowell B B, Fanselow M S, Wilson M A, Tonegawa S (2007). Dentate gyrus NMDA receptors mediate rapid pattern separation in the hippocampal network. Science, 317(5834): 94–99
doi: 10.1126/science.1140263 pmid: 17556551
127 Mignone J L, Kukekov V, Chiang A S, Steindler D, Enikolopov G (2004). Neural stem and progenitor cells in nestin-GFP transgenic mice. J Comp Neurol, 469(3): 311–324
doi: 10.1002/cne.10964 pmid: 14730584
128 Ming G L, Song H (2011). Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron, 70(4): 687–702
doi: 10.1016/j.neuron.2011.05.001 pmid: 21609825
129 Mitsuhashi T, Aoki Y, Eksioglu Y Z, Takahashi T, Bhide P G, Reeves S A, Caviness V S Jr (2001). Overexpression of p27Kip1 lengthens the G1 phase in a mouse model that targets inducible gene expression to central nervous system progenitor cells. Proc Natl Acad Sci USA, 98(11): 6435–6440
doi: 10.1073/pnas.111051398 pmid: 11371649
130 Miyagi S, Nishimoto M, Saito T, Ninomiya M, Sawamoto K, Okano H, Muramatsu M, Oguro H, Iwama A, Okuda A (2006). The Sox2 regulatory region 2 functions as a neural stem cell-specific enhancer in the telencephalon. J Biol Chem, 281(19): 13374–13381
doi: 10.1074/jbc.M512669200 pmid: 16547000
131 Mori T, Tanaka K, Buffo A, Wurst W, Kühn R, Götz M (2006). Inducible gene deletion in astroglia and radial glia—a valuable tool for functional and lineage analysis. Glia, 54(1): 21–34
doi: 10.1002/glia.20350 pmid: 16652340
132 Morshead C M, Reynolds B A, Craig C G, McBurney M W, Staines W A, Morassutti D, Weiss S, van der Kooy D (1994). Neural stem cells in the adult mammalian forebrain: a relatively quiescent subpopulation of subependymal cells. Neuron, 13(5): 1071–1082
doi: 10.1016/0896-6273(94)90046-9 pmid: 7946346
133 Mouret A, Lepousez G, Gras J, Gabellec M M, Lledo P M (2009). Turnover of newborn olfactory bulb neurons optimizes olfaction. J Neurosci, 29(39): 12302–12314
doi: 10.1523/JNEUROSCI.3383-09.2009 pmid: 19793989
134 Nakashiba T, Cushman J D, Pelkey K A, Renaudineau S, Buhl D L, McHugh T J, Rodriguez Barrera V, Chittajallu R, Iwamoto K S, McBain C J, Fanselow M S, Tonegawa S (2012). Young dentate granule cells mediate pattern separation, whereas old granule cells facilitate pattern completion. Cell, 149(1): 188–201
doi: 10.1016/j.cell.2012.01.046 pmid: 22365813
135 Namba T, Mochizuki H, Onodera M, Mizuno Y, Namiki H, Seki T (2005). The fate of neural progenitor cells expressing astrocytic and radial glial markers in the postnatal rat dentate gyrus. Eur J Neurosci, 22(8): 1928–1941
doi: 10.1111/j.1460-9568.2005.04396.x pmid: 16262632
136 Ninov N, Borius M, Stainier D Y (2012). Different levels of Notch signaling regulate quiescence, renewal and differentiation in pancreatic endocrine progenitors. Development, 139(9): 1557–1567
doi: 10.1242/dev.076000 pmid: 22492351
137 Nolte C, Matyash M, Pivneva T, Schipke C G, Ohlemeyer C, Hanisch U K, Kirchhoff F, Kettenmann H (2001). GFAP promoter-controlled EGFP-expressing transgenic mice: a tool to visualize astrocytes and astrogliosis in living brain tissue. Glia, 33(1): 72–86
doi: 10.1002/1098-1136(20010101)33:1<72::AID-GLIA1007>3.0.CO;2-A pmid: 11169793
138 Ohtsuka T, Sakamoto M, Guillemot F, Kageyama R (2001). Roles of the basic helix-loop-helix genes Hes1 and Hes5 in expansion of neural stem cells of the developing brain. J Biol Chem, 276(32): 30467–30474
doi: 10.1074/jbc.M102420200 pmid: 11399758
139 Palmer T D, Takahashi J, Gage F H (1997). The adult rat hippocampus contains primordial neural stem cells. Mol Cell Neurosci, 8(6): 389–404
doi: 10.1006/mcne.1996.0595 pmid: 9143557
140a Pan Y W, Chan G C, Kuo C T, Storm D R, Xia Z (2012). Inhibition of adult neurogenesis by inducible and targeted deletion of ERK5 mitogen-activated protein kinase specifically in adult neurogenic regions impairs contextual fear extinction and remote fear memory.J Neurosci, 32: 6444–6455
doi: 10.1073/pnas.0810407106 pmid: 19332781
140 Pastrana E, Cheng L C, Doetsch F (2009). Simultaneous prospective purification of adult subventricular zone neural stem cells and their progeny. Proc Natl Acad Sci USA, 106(15): 6387–6392
doi: 10.1073/pnas.0810407106 pmid: 19332781
141 Pereira A C, Huddleston D E, Brickman A M, Sosunov A A, Hen R, McKhann G M, Sloan R, Gage F H, Brown T R, Small S A (2007). An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus. Proc Natl Acad Sci USA, 104(13): 5638–5643
doi: 10.1073/pnas.0611721104 pmid: 17374720
142 Perl A K, Wert S E, Nagy A, Lobe C G, Whitsett J A (2002). Early restriction of peripheral and proximal cell lineages during formation of the lung. Proc Natl Acad Sci USA, 99(16): 10482–10487
doi: 10.1073/pnas.152238499 pmid: 12145322
143 Pevny L H, Sockanathan S, Placzek M, Lovell-Badge R (1998). A role for SOX1 in neural determination. Development, 125(10): 1967–1978
pmid: 9550729
144 Pimeisl I M, Tanriver Y, Daza R A, Vauti F, Hevner R F, Arnold H H, Arnold S J (2013). Generation and characterization of a tamoxifen-inducible Eomes(CreER) mouse line. Genesis, 51(10): 725–733
doi: 10.1002/dvg.22417 pmid: 23897762
145 Platel J C, Gordon V, Heintz T, Bordey A (2009). GFAP-GFP neural progenitors are antigenically homogeneous and anchored in their enclosed mosaic niche. Glia, 57(1): 66–78
doi: 10.1002/glia.20735 pmid: 18661547
146 Pollak J, Wilken M S, Ueki Y, Cox K E, Sullivan J M, Taylor R J, Levine E M, Reh T A (2013). ASCL1 reprograms mouse Muller glia into neurogenic retinal progenitors. Development, 140(12): 2619–2631
doi: 10.1242/dev.091355 pmid: 23637330
147 Quiñones-Hinojosa A, Sanai N, Soriano-Navarro M, Gonzalez-Perez O, Mirzadeh Z, Gil-Perotin S, Romero-Rodriguez R, Berger M S, Garcia-Verdugo J M, Alvarez-Buylla A (2006). Cellular composition and cytoarchitecture of the adult human subventricular zone: a niche of neural stem cells. J Comp Neurol, 494(3): 415–434
doi: 10.1002/cne.20798 pmid: 16320258
148 Raposo A A, Vasconcelos F F, Drechsel D, Marie C, Johnston C, Bithell A, Gillotin S, van den Berg D L, Ettwiller L, Flicek P, Crawford G E, Parras C M, Berninger B, Buckley N J, Guillemot F, Castro D S (2015). Ascl1 Coordinately Regulates Gene Expression and the Chromatin Landscape during Neurogenesis. Cell Rep, 10(9): 1–13
149 Regan M R, Huang Y H, Kim Y S, Dykes-Hoberg M I, Jin L, Watkins A M, Bergles D E, Rothstein J D (2007). Variations in promoter activity reveal a differential expression and physiology of glutamate transporters by glia in the developing and mature CNS. J Neurosci, 27(25): 6607–6619
doi: 10.1523/JNEUROSCI.0790-07.2007 pmid: 17581948
150 Sahay A, Hen R (2008). Hippocampal neurogenesis and depression. Novartis Found Symp 289, 152–160; discussion 160–154, 193–155
151a Sahay A, Scobie K N, Hill A S, O'Carroll C M, Kheirbek M A, Burghardt N S, Fenton A A, Dranovsky A, Hen R (2011). Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature, 472: 466–470
151 Sakamoto M, Ieki N, Miyoshi G, Mochimaru D, Miyachi H, Imura T, Yamaguchi M, Fishell G, Mori K, Kageyama R, Imayoshi I (2014). Continuous postnatal neurogenesis contributes to formation of the olfactory bulb neural circuits and flexible olfactory associative learning. J Neurosci, 34(17): 5788–5799
doi: 10.1523/JNEUROSCI.0674-14.2014 pmid: 24760839
152 Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, Weisstaub N, Lee J, Duman R, Arancio O, Belzung C, Hen R (2003). Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science, 301(5634): 805–809
doi: 10.1126/science.1083328 pmid: 12907793
153 Saxe M D, Battaglia F, Wang J W, Malleret G, David D J, Monckton J E, Garcia A D, Sofroniew M V, Kandel E R, Santarelli L, Hen R, Drew M R (2006). Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus. Proc Natl Acad Sci USA, 103(46): 17501–17506
doi: 10.1073/pnas.0607207103 pmid: 17088541
154 Schmid R S, Yokota Y, Anton E S (2006). Generation and characterization of brain lipid-binding protein promoter-based transgenic mouse models for the study of radial glia. Glia, 53(4): 345–351
doi: 10.1002/glia.20274 pmid: 16288463
155 Seri B, García-Verdugo J M, Collado-Morente L, McEwen B S, Alvarez-Buylla A (2004). Cell types, lineage, and architecture of the germinal zone in the adult dentate gyrus. J Comp Neurol, 478(4): 359–378
doi: 10.1002/cne.20288 pmid: 15384070
156 Seri B, García-Verdugo J M, McEwen B S, Alvarez-Buylla A (2001). Astrocytes give rise to new neurons in the adult mammalian hippocampus. J Neurosci, 21(18): 7153–7160
pmid: 11549726
157 Shen Q, Wang Y, Kokovay E, Lin G, Chuang S M, Goderie S K, Roysam B, Temple S (2008). Adult SVZ stem cells lie in a vascular niche: a quantitative analysis of niche cell-cell interactions. Cell Stem Cell, 3(3): 289–300
doi: 10.1016/j.stem.2008.07.026 pmid: 18786416
158 Shibata T, Watanabe M, Tanaka K, Wada K, Inoue Y (1996). Dynamic changes in expression of glutamate transporter mRNAs in developing brain. Neuroreport, 7(3): 705–709
doi: 10.1097/00001756-199602290-00006 pmid: 8733726
159 Shibata T, Yamada K, Watanabe M, Ikenaka K, Wada K, Tanaka K, Inoue Y (1997). Glutamate transporter GLAST is expressed in the radial glia-astrocyte lineage of developing mouse spinal cord. J Neurosci, 17(23): 9212–9219
pmid: 9364068
160 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 pmid: 18400163
161 Shin J, Berg D A, Zhu Y, Shin J Y, Song J, Bonaguidi M A, Enikolopov G, Nauen D W, Christian K M, Ming G L, Song H (2015). Single-Cell RNA-Seq with Waterfall Reveals Molecular Cascades underlying Adult Neurogenesis. Cell Stem Cell, 17(3): 360–372
doi: 10.1016/j.stem.2015.07.013 pmid: 26299571
162 Shors T J, Townsend D A, Zhao M, Kozorovitskiy Y, Gould E (2002). Neurogenesis may relate to some but not all types of hippocampal-dependent learning. Hippocampus, 12(5): 578–584
doi: 10.1002/hipo.10103 pmid: 12440573
163 Sierra A, Encinas J M, Maletic-Savatic M (2011). Adult human neurogenesis: from microscopy to magnetic resonance imaging. Front Neurosci, 5: 47
doi: 10.3389/fnins.2011.00047 pmid: 21519376
164 Slezak M, Göritz C, Niemiec A, Frisén J, Chambon P, Metzger D, Pfrieger F W (2007). Transgenic mice for conditional gene manipulation in astroglial cells. Glia, 55(15): 1565–1576
doi: 10.1002/glia.20570 pmid: 17823970
164a Snyder J S, Soumier A, Brewer M, Pickel J, Cameron H A (2011). Adult hippocampal neurogenesis buffers stress responses and depressive behaviour. Nature, 476: 458–461
165 Soriano P (1999). Generalized lacZ expression with the ROSA26 Cre reporter strain. Nat Genet, 21(1): 70–71
doi: 10.1038/5007 pmid: 9916792
166 Spalding K L, Bergmann O, Alkass K, Bernard S, Salehpour M, Huttner H B, Boström E, Westerlund I, Vial C, Buchholz B A, Possnert G, Mash D C, Druid H, Frisén J (2013). Dynamics of hippocampal neurogenesis in adult humans. Cell, 153(6): 1219–1227
doi: 10.1016/j.cell.2013.05.002 pmid: 23746839
167 Suh H, Consiglio A, Ray J, Sawai T, D’Amour K A, Gage F H (2007). In vivo fate analysis reveals the multipotent and self-renewal capacities of Sox2+ neural stem cells in the adult hippocampus. Cell Stem Cell, 1(5): 515–528
doi: 10.1016/j.stem.2007.09.002 pmid: 18371391
168 Sultan S, Gebara E, Toni N (2013). Doxycycline increases neurogenesis and reduces microglia in the adult hippocampus. Front Neurosci, 7: 131
pmid: 23898238
169 Sun M Y, Yetman M J, Lee T C, Chen Y, Jankowsky J L (2014). Specificity and efficiency of reporter expression in adult neural progenitors vary substantially among nestin-CreER(T2) lines. J Comp Neurol, 522(5): 1191–1208
doi: 10.1002/cne.23497 pmid: 24519019
170a Surget A, Tant A, Leonardo E D, Laugeray A, Rainer Q, Touma C, Palme R, Griebel G, Ibarguen-Vargas Y, Hen R, Belzung C (2011). Antidepressants recruit new neurons to improve stress response regulation. Mol Psychiatry, 16: 1177–1188
pmid: 8601800
170 Sutherland M L, Delaney T A, Noebels J L (1996). Glutamate transporter mRNA expression in proliferative zones of the developing and adult murine CNS. J Neurosci, 16(7): 2191–2207
pmid: 8601800
171 Takahashi K, Yamanaka S (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126(4): 663–676
doi: 10.1016/j.cell.2006.07.024 pmid: 16904174
172 Takeda N, Jain R, Leboeuf M R, Padmanabhan A, Wang Q, Li L, Lu M M, Millar S E, Epstein J A (2013). Hopx expression defines a subset of multipotent hair follicle stem cells and a progenitor population primed to give rise to K6+ niche cells. Development, 140(8): 1655–1664
doi: 10.1242/dev.093005 pmid: 23487314
173 Takeda N, Jain R, LeBoeuf M R, Wang Q, Lu M M, Epstein J A (2011). Interconversion between intestinal stem cell populations in distinct niches. Science, 334(6061): 1420–1424
doi: 10.1126/science.1213214 pmid: 22075725
174 Tavazoie M, Van der Veken L, Silva-Vargas V, Louissaint M, Colonna L, Zaidi B, Garcia-Verdugo J M, Doetsch F (2008). A specialized vascular niche for adult neural stem cells. Cell Stem Cell, 3(3): 279–288
doi: 10.1016/j.stem.2008.07.025 pmid: 18786415
175 Tseng Y Y, Gruzdeva N, Li A, Chuang J Z, Sung C H (2010). Identification of the Tctex-1 regulatory element that directs expression to neural stem/progenitor cells in developing and adult brain. J Comp Neurol, 518(16): 3327–3342
doi: 10.1002/cne.22402 pmid: 20575070
176 Uwanogho D, Rex M, Cartwright E J, Pearl G, Healy C, Scotting P J, Sharpe P T (1995). Embryonic expression of the chicken Sox2, Sox3 and Sox11 genes suggests an interactive role in neuronal development. Mech Dev, 49(1-2): 23–36
doi: 10.1016/0925-4773(94)00299-3 pmid: 7748786
177 Venere M, Han Y G, Bell R, Song J S, Alvarez-Buylla A, Blelloch R (2012). Sox1 marks an activated neural stem/progenitor cell in the hippocampus. Development, 139(21): 3938–3949
doi: 10.1242/dev.081133 pmid: 22992951
178 Vierbuchen T, Ostermeier A, Pang Z P, Kokubu Y, Südhof T C, Wernig M (2010). Direct conversion of fibroblasts to functional neurons by defined factors. Nature, 463(7284): 1035–1041
doi: 10.1038/nature08797 pmid: 20107439
179 Walker T L, Overall R W, Vogler S, Sykes A M, Ruhwald S, Lasse D, Ichwan M, Fabel K, Kempermann G (2016). Lysophosphatidic acid receptor is a functional marker of adult hippocampal precursor cells. Stem Cell Rep, 6(4): 552–565
doi: 10.1016/j.stemcr.2016.03.002 pmid: 27050949
180 Walker T L, Yasuda T, Adams D J, Bartlett P F (2007). The doublecortin-expressing population in the developing and adult brain contains multipotential precursors in addition to neuronal-lineage cells. J Neurosci, 27(14): 3734–3742
doi: 10.1523/JNEUROSCI.5060-06.2007 pmid: 17409237
181 Wang X, Qiu R, Tsark W, Lu Q (2007). Rapid promoter analysis in developing mouse brain and genetic labeling of young neurons by doublecortin-DsRed-express. J Neurosci Res, 85(16): 3567–3573
doi: 10.1002/jnr.21440 pmid: 17671991
182 Wiese C, Rolletschek A, Kania G, Blyszczuk P, Tarasov K V, Tarasova Y, Wersto R P, Boheler K R, Wobus A M (2004). Nestin expression—a property of multi-lineage progenitor cells? Cell Mol Life Sci, 61(19-20): 2510–2522
doi: 10.1007/s00018-004-4144-6 pmid: 15526158
183 Williams S M, Sullivan R K, Scott H L, Finkelstein D I, Colditz P B, Lingwood B E, Dodd P R, Pow D V (2005). Glial glutamate transporter expression patterns in brains from multiple mammalian species. Glia, 49(4): 520–541
doi: 10.1002/glia.20139 pmid: 15578656
183a Wojtowicz J M, Askew M L, Winocur G (2008). The effects of running and of inhibiting adult neurogenesis on learning and memory in rats. Eur J Neurosci, 27: 1494–1502
184 Yamaguchi M, Saito H, Suzuki M, Mori K (2000). Visualization of neurogenesis in the central nervous system using nestin promoter-GFP transgenic mice. Neuroreport, 11(9): 1991–1996
doi: 10.1097/00001756-200006260-00037 pmid: 10884058
185 Yang S M, Alvarez D D, Schinder A F (2015). Reliable Genetic Labeling of Adult-Born Dentate Granule Cells Using Ascl1 CreERT2 and Glast CreERT2 Murine Lines. J Neurosci, 35(46): 15379–15390
doi: 10.1523/JNEUROSCI.2345-15.2015 pmid: 26586824
186 Yaworsky P J, Kappen C (1999). Heterogeneity of neural progenitor cells revealed by enhancers in the nestin gene. Dev Biol, 205(2): 309–321
doi: 10.1006/dbio.1998.9035 pmid: 9917366
187 Yu T S, Dandekar M, Monteggia L M, Parada L F, Kernie S G (2005). Temporally regulated expression of Cre recombinase in neural stem cells. Genesis, 41(4): 147–153
doi: 10.1002/gene.20110 pmid: 15789426
188 Zappone M V, Galli R, Catena R, Meani N, De Biasi S, Mattei E, Tiveron C, Vescovi A L, Lovell-Badge R, Ottolenghi S, Nicolis S K (2000). Sox2 regulatory sequences direct expression of a (beta)-geo transgene to telencephalic neural stem cells and precursors of the mouse embryo, revealing regionalization of gene expression in CNS stem cells. Development, 127(11): 2367–2382
pmid: 10804179
189 Zecevic N (2004). Specific characteristic of radial glia in the human fetal telencephalon. Glia, 48(1): 27–35
doi: 10.1002/glia.20044 pmid: 15326612
190 Zhang C L, Zou Y, He W, Gage F H, Evans R M (2008). A role for adult TLX-positive neural stem cells in learning and behaviour. Nature, 451(7181): 1004–1007
doi: 10.1038/nature06562 pmid: 18235445
191 Zhao C, Deng W, Gage F H (2008). Mechanisms and functional implications of adult neurogenesis. Cell, 132(4): 645–660
doi: 10.1016/j.cell.2008.01.033 pmid: 18295581
192 Zhuo L, Sun B, Zhang C L, Fine A, Chiu S Y, Messing A (1997). Live astrocytes visualized by green fluorescent protein in transgenic mice. Dev Biol, 187(1): 36–42
doi: 10.1006/dbio.1997.8601 pmid: 9224672
193 Zimmerman L, Parr B, Lendahl U, Cunningham M, McKay R, Gavin B, Mann J, Vassileva G, McMahon A (1994). Independent regulatory elements in the nestin gene direct transgene expression to neural stem cells or muscle precursors. Neuron, 12(1): 11–24
doi: 10.1016/0896-6273(94)90148-1 pmid: 8292356
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