메뉴 건너뛰기




Volumn 76, Issue 7, 2016, Pages 748-763

Characterization and isolation of immature neurons of the adult mouse piriform cortex

Author keywords

adult neurogenesis; neuroblast; neuronal birthdating; proliferation; PSA NCAM

Indexed keywords

NERVE CELL ADHESION MOLECULE; NUCLEOSIDE; THYMIDINE DERIVATIVE;

EID: 84973619433     PISSN: 19328451     EISSN: 1932846X     Source Type: Journal    
DOI: 10.1002/dneu.22357     Document Type: Article
Times cited : (28)

References (56)
  • 2
    • 84860450524 scopus 로고    scopus 로고
    • A protocol for isolation and enriched monolayer cultivation of neural precursor cells from mouse dentate gyrus
    • Babu H, Claasen JH, Kannan S, Runker AE, Palmer T, Kempermann G. 2011. A protocol for isolation and enriched monolayer cultivation of neural precursor cells from mouse dentate gyrus. Front Neurosci 5:89.
    • (2011) Front Neurosci , vol.5 , pp. 89
    • Babu, H.1    Claasen, J.H.2    Kannan, S.3    Runker, A.E.4    Palmer, T.5    Kempermann, G.6
  • 3
    • 0022851569 scopus 로고
    • Neurogenesis in the rat primary olfactory cortex
    • Bayer SA. 1986. Neurogenesis in the rat primary olfactory cortex. Int J Dev Neurosci 4:251–271.
    • (1986) Int J Dev Neurosci , vol.4 , pp. 251-271
    • Bayer, S.A.1
  • 4
    • 84879783874 scopus 로고    scopus 로고
    • Neurons and circuits for odor processing in the piriform cortex
    • Bekkers JM, Suzuki N. 2013. Neurons and circuits for odor processing in the piriform cortex. Trends Neurosci 36:429–438.
    • (2013) Trends Neurosci , vol.36 , pp. 429-438
    • Bekkers, J.M.1    Suzuki, N.2
  • 5
    • 0037437148 scopus 로고    scopus 로고
    • Postnatal NG2 proteoglycan-expressing progenitor cells are intrinsically multipotent and generate functional neurons
    • Belachew S, Chittajallu R, Aguirre AA, Yuan X, Kirby M, Anderson S, Gallo V. 2003. Postnatal NG2 proteoglycan-expressing progenitor cells are intrinsically multipotent and generate functional neurons. J Cell Biol 161:169–186.
    • (2003) J Cell Biol , vol.161 , pp. 169-186
    • Belachew, S.1    Chittajallu, R.2    Aguirre, A.A.3    Yuan, X.4    Kirby, M.5    Anderson, S.6    Gallo, V.7
  • 7
    • 0037143741 scopus 로고    scopus 로고
    • Newly generated neurons in the amygdala and adjoining cortex of adult primates
    • Bernier PJ, Bedard A, Vinet J, Levesque M, Parent A. 2002. Newly generated neurons in the amygdala and adjoining cortex of adult primates. Proc Natl Acad Sci USA 99:11464–11469.
    • (2002) Proc Natl Acad Sci USA , vol.99 , pp. 11464-11469
    • Bernier, P.J.1    Bedard, A.2    Vinet, J.3    Levesque, M.4    Parent, A.5
  • 8
    • 84861611930 scopus 로고    scopus 로고
    • New scenarios for neuronal structural plasticity in non-neurogenic brain parenchyma: The case of cortical layer II immature neurons
    • Bonfanti L, Nacher J. 2012. New scenarios for neuronal structural plasticity in non-neurogenic brain parenchyma: The case of cortical layer II immature neurons. Prog Neurobiol 98:1–15.
    • (2012) Prog Neurobiol , vol.98 , pp. 1-15
    • Bonfanti, L.1    Nacher, J.2
  • 9
    • 0028049767 scopus 로고
    • Expression of polysialylated neural cell adhesion molecule by proliferating cells in the subependymal layer of the adult rat, in its rostral extension and in the olfactory bulb
    • Bonfanti L, Theodosis DT. 1994. Expression of polysialylated neural cell adhesion molecule by proliferating cells in the subependymal layer of the adult rat, in its rostral extension and in the olfactory bulb. Neuroscience 62:291–305.
    • (1994) Neuroscience , vol.62 , pp. 291-305
    • Bonfanti, L.1    Theodosis, D.T.2
  • 10
    • 34250718676 scopus 로고    scopus 로고
    • Isolation and culture of adult neurons and neurospheres
    • Brewer GJ, Torricelli JR. 2007. Isolation and culture of adult neurons and neurospheres. Nat Protoc 2:1490–1498.
    • (2007) Nat Protoc , vol.2 , pp. 1490-1498
    • Brewer, G.J.1    Torricelli, J.R.2
  • 11
    • 62049084650 scopus 로고    scopus 로고
    • Doublecortin expression in adult cat and primate cerebral cortex relates to immature neurons that develop into GABAergic subgroups
    • Cai Y, Xiong K, Chu Y, Luo DW, Luo XG, Yuan XY, Struble RG, et al. 2009. Doublecortin expression in adult cat and primate cerebral cortex relates to immature neurons that develop into GABAergic subgroups. Exp Neurol 216:342–356.
    • (2009) Exp Neurol , vol.216 , pp. 342-356
    • Cai, Y.1    Xiong, K.2    Chu, Y.3    Luo, D.W.4    Luo, X.G.5    Yuan, X.Y.6    Struble, R.G.7
  • 12
    • 33846571886 scopus 로고    scopus 로고
    • The origin and cell lineage of microglia: New concepts
    • Chan WY, Kohsaka S, Rezaie P. 2007. The origin and cell lineage of microglia: New concepts. Brain Res Rev 53:344–354.
    • (2007) Brain Res Rev , vol.53 , pp. 344-354
    • Chan, W.Y.1    Kohsaka, S.2    Rezaie, P.3
  • 13
    • 65449143961 scopus 로고    scopus 로고
    • Inducible site-specific recombination in neural stem/progenitor cells
    • Chen J, Kwon CH, Lin L, Li Y, Parada LF. 2009. Inducible site-specific recombination in neural stem/progenitor cells. Genesis 47:122–131.
    • (2009) Genesis , vol.47 , pp. 122-131
    • Chen, J.1    Kwon, C.H.2    Lin, L.3    Li, Y.4    Parada, L.F.5
  • 14
    • 13444309241 scopus 로고    scopus 로고
    • New GABAergic interneurons in the adult neocortex and striatum are generated from different precursors
    • Dayer AG, Cleaver KM, Abouantoun T, Cameron HA. 2005. New GABAergic interneurons in the adult neocortex and striatum are generated from different precursors. J Cell Biol 168:415–427.
    • (2005) J Cell Biol , vol.168 , pp. 415-427
    • Dayer, A.G.1    Cleaver, K.M.2    Abouantoun, T.3    Cameron, H.A.4
  • 16
    • 12144266963 scopus 로고    scopus 로고
    • Pax6, Tbr2, and Tbr1 are expressed sequentially by radial glia, intermediate progenitor cells, and postmitotic neurons in developing neocortex
    • Englund C, Fink A, Lau C, Pham D, Daza RA, Bulfone A, Kowalczyk T, et al. 2005. Pax6, Tbr2, and Tbr1 are expressed sequentially by radial glia, intermediate progenitor cells, and postmitotic neurons in developing neocortex. J Neurosci 25:247–251.
    • (2005) J Neurosci , vol.25 , pp. 247-251
    • Englund, C.1    Fink, A.2    Lau, C.3    Pham, D.4    Daza, R.A.5    Bulfone, A.6    Kowalczyk, T.7
  • 18
    • 0033153135 scopus 로고    scopus 로고
    • Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons
    • Francis F, Koulakoff A, Boucher D, Chafey P, Schaar B, Vinet MC, Friocourt G, et al. 1999. Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons. Neuron 23:247–256.
    • (1999) Neuron , vol.23 , pp. 247-256
    • Francis, F.1    Koulakoff, A.2    Boucher, D.3    Chafey, P.4    Schaar, B.5    Vinet, M.C.6    Friocourt, G.7
  • 20
    • 0033152450 scopus 로고    scopus 로고
    • Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons
    • Gleeson JG, Lin PT, Flanagan LA, Walsh CA. 1999. Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons. Neuron 23:257–271.
    • (1999) Neuron , vol.23 , pp. 257-271
    • Gleeson, J.G.1    Lin, P.T.2    Flanagan, L.A.3    Walsh, C.A.4
  • 22
    • 79953703974 scopus 로고    scopus 로고
    • Olfactory bulbectomy, but not odor conditioned aversion, induces the differentiation of immature neurons in the adult rat piriform cortex
    • Gomez-Climent MA, Hernandez-Gonzalez S, Shionoya K, Belles M, Alonso-Llosa G, Datiche F, Nacher J. 2011. Olfactory bulbectomy, but not odor conditioned aversion, induces the differentiation of immature neurons in the adult rat piriform cortex. Neuroscience 181:18–27.
    • (2011) Neuroscience , vol.181 , pp. 18-27
    • Gomez-Climent, M.A.1    Hernandez-Gonzalez, S.2    Shionoya, K.3    Belles, M.4    Alonso-Llosa, G.5    Datiche, F.6    Nacher, J.7
  • 23
    • 77956594507 scopus 로고    scopus 로고
    • Pyramidal neurons are generated from oligodendroglial progenitor cells in adult piriform cortex
    • Guo F, Maeda Y, Ma J, Xu J, Horiuchi M, Miers L, Vaccarino F, et al. 2010. Pyramidal neurons are generated from oligodendroglial progenitor cells in adult piriform cortex. J Neurosci 30:12036–12049.
    • (2010) J Neurosci , vol.30 , pp. 12036-12049
    • Guo, F.1    Maeda, Y.2    Ma, J.3    Xu, J.4    Horiuchi, M.5    Miers, L.6    Vaccarino, F.7
  • 24
    • 0020658761 scopus 로고
    • Structure of the piriform cortex of the opossum. I. Description of neuron types with Golgi methods
    • Haberly LB. 1983. Structure of the piriform cortex of the opossum. I. Description of neuron types with Golgi methods. J Comp Neurol 213:163–187.
    • (1983) J Comp Neurol , vol.213 , pp. 163-187
    • Haberly, L.B.1
  • 25
    • 0032143165 scopus 로고    scopus 로고
    • Generating green fluorescent mice by germline transmission of green fluorescent ES cells
    • Hadjantonakis AK, Gertsenstein M, Ikawa M, Okabe M, Nagy A. 1998. Generating green fluorescent mice by germline transmission of green fluorescent ES cells. Mech Dev 76:79–90.
    • (1998) Mech Dev , vol.76 , pp. 79-90
    • Hadjantonakis, A.K.1    Gertsenstein, M.2    Ikawa, M.3    Okabe, M.4    Nagy, A.5
  • 26
    • 84891327211 scopus 로고    scopus 로고
    • Olfactory experience modulates immature neuron development in postnatal and adult guinea pig piriform cortex
    • He X, Zhang XM, Wu J, Fu J, Mou L, Lu DH, Cai Y, et al. 2014. Olfactory experience modulates immature neuron development in postnatal and adult guinea pig piriform cortex. Neuroscience 259:101–112.
    • (2014) Neuroscience , vol.259 , pp. 101-112
    • He, X.1    Zhang, X.M.2    Wu, J.3    Fu, J.4    Mou, L.5    Lu, D.H.6    Cai, Y.7
  • 27
    • 84898038230 scopus 로고    scopus 로고
    • Novel NG2-CreERT2 knock-in mice demonstrate heterogeneous differentiation potential of NG2 glia during development
    • Huang W, Zhao N, Bai X, Karram K, Trotter J, Goebbels S, Scheller A, et al. 2014. Novel NG2-CreERT2 knock-in mice demonstrate heterogeneous differentiation potential of NG2 glia during development. Glia 62:896–913.
    • (2014) Glia , vol.62 , pp. 896-913
    • Huang, W.1    Zhao, N.2    Bai, X.3    Karram, K.4    Trotter, J.5    Goebbels, S.6    Scheller, A.7
  • 28
    • 0037196872 scopus 로고    scopus 로고
    • The utility of Ki-67 and BrdU as proliferative markers of adult neurogenesis
    • Kee N, Sivalingam S, Boonstra R, Wojtowicz JM. 2002. The utility of Ki-67 and BrdU as proliferative markers of adult neurogenesis. J Neurosci Methods 115:97–105.
    • (2002) J Neurosci Methods , vol.115 , pp. 97-105
    • Kee, N.1    Sivalingam, S.2    Boonstra, R.3    Wojtowicz, J.M.4
  • 29
    • 80054057427 scopus 로고    scopus 로고
    • Properties of doublecortin-(DCX)-expressing cells in the piriform cortex compared to the neurogenic dentate gyrus of adult mice
    • Klempin F, Kronenberg G, Cheung G, Kettenmann H, Kempermann G. 2011. Properties of doublecortin-(DCX)-expressing cells in the piriform cortex compared to the neurogenic dentate gyrus of adult mice. PLoS One 6:e25760
    • (2011) PLoS One , vol.6
    • Klempin, F.1    Kronenberg, G.2    Cheung, G.3    Kettenmann, H.4    Kempermann, G.5
  • 30
    • 0035885342 scopus 로고    scopus 로고
    • The fates of cells generated at the end of neurogenesis in developing mouse cortex
    • Levers TE, Edgar JM, Price DJ. 2001. The fates of cells generated at the end of neurogenesis in developing mouse cortex. J Neurobiol 48:265–277.
    • (2001) J Neurobiol , vol.48 , pp. 265-277
    • Levers, T.E.1    Edgar, J.M.2    Price, D.J.3
  • 31
    • 67649227034 scopus 로고    scopus 로고
    • DCX and PSA-NCAM expression identifies a population of neurons preferentially distributed in associative areas of different pallial derivatives and vertebrate species
    • Luzzati F, Bonfanti L, Fasolo A, Peretto P. 2009. DCX and PSA-NCAM expression identifies a population of neurons preferentially distributed in associative areas of different pallial derivatives and vertebrate species. Cereb Cortex 19:1028–1041.
    • (2009) Cereb Cortex , vol.19 , pp. 1028-1041
    • Luzzati, F.1    Bonfanti, L.2    Fasolo, A.3    Peretto, P.4
  • 33
    • 0026697724 scopus 로고
    • NeuN, a neuronal specific nuclear protein in vertebrates
    • Mullen RJ, Buck CR, Smith AM. 1992. NeuN, a neuronal specific nuclear protein in vertebrates. Development 116:201–211.
    • (1992) Development , vol.116 , pp. 201-211
    • Mullen, R.J.1    Buck, C.R.2    Smith, A.M.3
  • 34
    • 0037081519 scopus 로고    scopus 로고
    • PSA-NCAM expression in the piriform cortex of the adult rat. Modulation by NMDA receptor antagonist administration
    • Nacher J, Alonso-Llosa G, Rosell D, McEwen B. 2002. PSA-NCAM expression in the piriform cortex of the adult rat. Modulation by NMDA receptor antagonist administration. Brain Res 927:111–121.
    • (2002) Brain Res , vol.927 , pp. 111-121
    • Nacher, J.1    Alonso-Llosa, G.2    Rosell, D.3    McEwen, B.4
  • 35
    • 0036283521 scopus 로고    scopus 로고
    • Doublecortin expression in the adult rat telencephalon
    • Nacher J, Crespo C, McEwen BS. 2001. Doublecortin expression in the adult rat telencephalon. Eur J Neurosci 14:629–644.
    • (2001) Eur J Neurosci , vol.14 , pp. 629-644
    • Nacher, J.1    Crespo, C.2    McEwen, B.S.3
  • 36
    • 0032948065 scopus 로고    scopus 로고
    • Polysialylated neural cell adhesion molecule expression in the dentate gyrus of the human hippocampal formation from infancy to old age
    • Ni Dhuill CM, Fox GB, Pittock SJ, O'Connell AW, Murphy KJ, Regan CM. 1999. Polysialylated neural cell adhesion molecule expression in the dentate gyrus of the human hippocampal formation from infancy to old age. J Neurosci Res 55:99–106.
    • (1999) J Neurosci Res , vol.55 , pp. 99-106
    • Ni Dhuill, C.M.1    Fox, G.B.2    Pittock, S.J.3    O'Connell, A.W.4    Murphy, K.J.5    Regan, C.M.6
  • 37
    • 0028895098 scopus 로고
    • FGF-2-responsive neuronal progenitors reside in proliferative and quiescent regions of the adult rodent brain
    • Palmer TD, Ray J, Gage FH. 1995. FGF-2-responsive neuronal progenitors reside in proliferative and quiescent regions of the adult rodent brain. Mol Cell Neurosci 6:474–486.
    • (1995) Mol Cell Neurosci , vol.6 , pp. 474-486
    • Palmer, T.D.1    Ray, J.2    Gage, F.H.3
  • 38
    • 33646361842 scopus 로고    scopus 로고
    • Neurogenesis in the adult rat piriform cortex
    • Pekcec A, Loscher W, Potschka H. 2006. Neurogenesis in the adult rat piriform cortex. Neuroreport 17:571–574.
    • (2006) Neuroreport , vol.17 , pp. 571-574
    • Pekcec, A.1    Loscher, W.2    Potschka, H.3
  • 39
    • 0035449745 scopus 로고    scopus 로고
    • Infusion of brain-derived neurotrophic factor into the lateral ventricle of the adult rat leads to new neurons in the parenchyma of the striatum, septum, thalamus, and hypothalamus
    • Pencea V, Bingaman KD, Wiegand SJ, Luskin MB. 2001. Infusion of brain-derived neurotrophic factor into the lateral ventricle of the adult rat leads to new neurons in the parenchyma of the striatum, septum, thalamus, and hypothalamus. J Neurosci 21:6706–6717.
    • (2001) J Neurosci , vol.21 , pp. 6706-6717
    • Pencea, V.1    Bingaman, K.D.2    Wiegand, S.J.3    Luskin, M.B.4
  • 40
    • 1842689270 scopus 로고    scopus 로고
    • Purification of neuronal precursors from the adult mouse brain: Comprehensive gene expression analysis provides new insights into the control of cell migration, differentiation, and homeostasis
    • Pennartz S, Belvindrah R, Tomiuk S, Zimmer C, Hofmann K, Conradt M, Bosio A, et al. 2004. Purification of neuronal precursors from the adult mouse brain: Comprehensive gene expression analysis provides new insights into the control of cell migration, differentiation, and homeostasis. Mol Cell Neurosci 25:692–706.
    • (2004) Mol Cell Neurosci , vol.25 , pp. 692-706
    • Pennartz, S.1    Belvindrah, R.2    Tomiuk, S.3    Zimmer, C.4    Hofmann, K.5    Conradt, M.6    Bosio, A.7
  • 41
    • 0026535505 scopus 로고
    • Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system
    • Reynolds BA, Weiss S. 1992. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255:1707–1710.
    • (1992) Science , vol.255 , pp. 1707-1710
    • Reynolds, B.A.1    Weiss, S.2
  • 42
    • 79956221125 scopus 로고    scopus 로고
    • NG2-glia as multipotent neural stem cells: Fact or fantasy?
    • Richardson WD, Young KM, Tripathi RB, McKenzie I. 2011. NG2-glia as multipotent neural stem cells: Fact or fantasy? Neuron 70:661–673.
    • (2011) Neuron , vol.70 , pp. 661-673
    • Richardson, W.D.1    Young, K.M.2    Tripathi, R.B.3    McKenzie, I.4
  • 43
    • 56749156453 scopus 로고    scopus 로고
    • PDGFRA/NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice
    • Rivers LE, Young KM, Rizzi M, Jamen F, Psachoulia K, Wade A, Kessaris N, et al. 2008. PDGFRA/NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice. Nat Neurosci 11:1392–1401.
    • (2008) Nat Neurosci , vol.11 , pp. 1392-1401
    • Rivers, L.E.1    Young, K.M.2    Rizzi, M.3    Jamen, F.4    Psachoulia, K.5    Wade, A.6    Kessaris, N.7
  • 44
    • 79957456435 scopus 로고    scopus 로고
    • Developmental dynamics of piriform cortex
    • Sarma AA, Richard MB, Greer CA. 2011. Developmental dynamics of piriform cortex. Cereb Cortex 21:1231–1245.
    • (2011) Cereb Cortex , vol.21 , pp. 1231-1245
    • Sarma, A.A.1    Richard, M.B.2    Greer, C.A.3
  • 47
    • 33744999832 scopus 로고    scopus 로고
    • Glial conversion of SVZ-derived committed neuronal precursors after ectopic grafting into the adult brain
    • Seidenfaden R, Desoeuvre A, Bosio A, Virard I, Cremer H. 2006. Glial conversion of SVZ-derived committed neuronal precursors after ectopic grafting into the adult brain. Mol Cell Neurosci 32:187–198.
    • (2006) Mol Cell Neurosci , vol.32 , pp. 187-198
    • Seidenfaden, R.1    Desoeuvre, A.2    Bosio, A.3    Virard, I.4    Cremer, H.5
  • 49
    • 34250167942 scopus 로고    scopus 로고
    • Olfactory enrichment enhances the survival of newly born cortical neurons in adult mice
    • Shapiro LA, Ng KL, Zhou QY, Ribak CE. 2007. Olfactory enrichment enhances the survival of newly born cortical neurons in adult mice. Neuroreport 18:981–985.
    • (2007) Neuroreport , vol.18 , pp. 981-985
    • Shapiro, L.A.1    Ng, K.L.2    Zhou, Q.Y.3    Ribak, C.E.4
  • 51
    • 34347368939 scopus 로고    scopus 로고
    • Multi-directional differentiation of doublecortin- and NG2-immunopositive progenitor cells in the adult rat neocortex in vivo
    • Tamura Y, Kataoka Y, Cui Y, Takamori Y, Watanabe Y, Yamada H. 2007. Multi-directional differentiation of doublecortin- and NG2-immunopositive progenitor cells in the adult rat neocortex in vivo. Eur J Neurosci 25:3489–3498.
    • (2007) Eur J Neurosci , vol.25 , pp. 3489-3498
    • Tamura, Y.1    Kataoka, Y.2    Cui, Y.3    Takamori, Y.4    Watanabe, Y.5    Yamada, H.6
  • 54
    • 42749093186 scopus 로고    scopus 로고
    • Doublecortin-expressing cells are present in layer II across the adult guinea pig cerebral cortex: Partial colocalization with mature interneuron markers
    • Xiong K, Luo DW, Patrylo PR, Luo XG, Struble RG, Clough RW, Yan XX. 2008. Doublecortin-expressing cells are present in layer II across the adult guinea pig cerebral cortex: Partial colocalization with mature interneuron markers. Exp Neurol 211:271–282.
    • (2008) Exp Neurol , vol.211 , pp. 271-282
    • Xiong, K.1    Luo, D.W.2    Patrylo, P.R.3    Luo, X.G.4    Struble, R.G.5    Clough, R.W.6    Yan, X.X.7
  • 55
    • 0346655312 scopus 로고    scopus 로고
    • Microglia, a potential source of neurons, astrocytes, and oligodendrocytes
    • Yokoyama A, Yang L, Itoh S, Mori K, Tanaka J. 2004. Microglia, a potential source of neurons, astrocytes, and oligodendrocytes. Glia 45:96–104.
    • (2004) Glia , vol.45 , pp. 96-104
    • Yokoyama, A.1    Yang, L.2    Itoh, S.3    Mori, K.4    Tanaka, J.5
  • 56
    • 79960863140 scopus 로고    scopus 로고
    • Doublecortin-expressing cells persist in the associative cerebral cortex and amygdala in aged nonhuman primates
    • Zhang XM, Cai Y, Chu Y, Chen EY, Feng JC, Luo XG, Xiong K, et al. 2009. Doublecortin-expressing cells persist in the associative cerebral cortex and amygdala in aged nonhuman primates. Front Neuroanat 3:17.
    • (2009) Front Neuroanat , vol.3 , pp. 17
    • Zhang, X.M.1    Cai, Y.2    Chu, Y.3    Chen, E.Y.4    Feng, J.C.5    Luo, X.G.6    Xiong, K.7


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.