메뉴 건너뛰기




Volumn 131, Issue 22, 2004, Pages 5539-5550

Hes genes regulate size, shape and histogenesis of the nervous system by control of the timing of neural stem cell differentiation

Author keywords

Adherens junction; Basal lamina; bHLH; Neuroepithelium; Radial glia; Tight junction

Indexed keywords

CELL PROTEIN; NOTCH RECEPTOR; PROTEIN HES; PROTEIN HES3; PROTEIN HES5; TRANSCRIPTION FACTOR HES 1; UNCLASSIFIED DRUG;

EID: 10344264425     PISSN: 09501991     EISSN: None     Source Type: Journal    
DOI: 10.1242/dev.01436     Document Type: Article
Times cited : (496)

References (63)
  • 1
    • 0030589622 scopus 로고    scopus 로고
    • Loss of occludin and functional tight junctions, but not Z0-1, during neural tube closure - Remodeling of the neuroepithelium prior to neurogenesis
    • Aaku-Saraste, E., Hellwig, A. and Huttner, W. B. (1996). Loss of occludin and functional tight junctions, but not Z0-1, during neural tube closure - remodeling of the neuroepithelium prior to neurogenesis. Dev. Biol. 180, 664-679.
    • (1996) Dev. Biol. , vol.180 , pp. 664-679
    • Aaku-Saraste, E.1    Hellwig, A.2    Huttner, W.B.3
  • 2
    • 2042509704 scopus 로고    scopus 로고
    • A comparison of Notch, Hes and Grg expression during murine embryonic and post-natal development
    • Allen, T. and Lobe, C. G. (1999). A comparison of Notch, Hes and Grg expression during murine embryonic and post-natal development. Cell. Mol. Biol. 45, 687-708.
    • (1999) Cell. Mol. Biol. , vol.45 , pp. 687-708
    • Allen, T.1    Lobe, C.G.2
  • 3
    • 0033617522 scopus 로고    scopus 로고
    • Notch signaling: Cell fate control and signal integration in development
    • Artavanis-Tsakonas, S., Rand, M. D. and Lake, R. J. (1999). Notch signaling: cell fate control and signal integration in development. Science 284, 770-776.
    • (1999) Science , vol.284 , pp. 770-776
    • Artavanis-Tsakonas, S.1    Rand, M.D.2    Lake, R.J.3
  • 4
    • 0016723881 scopus 로고
    • Differentiation of the neural plate and neural tube in the young chick embryo
    • Bancroft, M. and Bellairs, R. (1975). Differentiation of the neural plate and neural tube in the young chick embryo. Anat. Embryol. 147, 309-335.
    • (1975) Anat. Embryol. , vol.147 , pp. 309-335
    • Bancroft, M.1    Bellairs, R.2
  • 5
    • 0026698879 scopus 로고
    • Effects of antibodies against N-cadherin and N-CAM on the cranial neural crest and neural tube
    • Bronner-Fraser, M., Wolf, J. J. and Murray, B. A. (1992). Effects of antibodies against N-cadherin and N-CAM on the cranial neural crest and neural tube. Dev. Biol. 153, 291-301.
    • (1992) Dev. Biol. , vol.153 , pp. 291-301
    • Bronner-Fraser, M.1    Wolf, J.J.2    Murray, B.A.3
  • 6
    • 13344249785 scopus 로고    scopus 로고
    • Ocular retardation mouse caused by Chx10 homeobox null allele: Impaired retinal progenitor proliferation and bipolar cell differentiation
    • Burmeister, M., Novak, J., Liang, M.-Y., Basu, S., Ploder, L., Hawes, N. L., Vidgen, D., Hoover, F., Goldman, D., Kalnins, V. I. et al. (1996). Ocular retardation mouse caused by Chx10 homeobox null allele: impaired retinal progenitor proliferation and bipolar cell differentiation. Nat. Genet. 12, 376-384.
    • (1996) Nat. Genet. , vol.12 , pp. 376-384
    • Burmeister, M.1    Novak, J.2    Liang, M.-Y.3    Basu, S.4    Ploder, L.5    Hawes, N.L.6    Vidgen, D.7    Hoover, F.8    Goldman, D.9    Kalnins, V.I.10
  • 7
    • 0033852950 scopus 로고    scopus 로고
    • HES-1 repression of differentiation and proliferationin PC12 cells: Role for the helix 3-helix 4 domain in transcription repression
    • Castella, P., Sawai, S., Nakao, K., Wagner, J. A. and Caudy, M. (2000). HES-1 repression of differentiation and proliferationin PC12 cells: role for the helix 3-helix 4 domain in transcription repression. Mol. Cell. Biol. 20, 6170-6183.
    • (2000) Mol. Cell. Biol. , vol.20 , pp. 6170-6183
    • Castella, P.1    Sawai, S.2    Nakao, K.3    Wagner, J.A.4    Caudy, M.5
  • 8
    • 0034122226 scopus 로고    scopus 로고
    • Hes genes regulate sequential stages of neurogenesis in the olfactory epithelium
    • Cau, E., Gradwohl, G., Casarosa, S., Kageyama, R. and Guillemot, F. (2000). Hes genes regulate sequential stages of neurogenesis in the olfactory epithelium. Development 127, 2323-2332.
    • (2000) Development , vol.127 , pp. 2323-2332
    • Cau, E.1    Gradwohl, G.2    Casarosa, S.3    Kageyama, R.4    Guillemot, F.5
  • 9
    • 0037135177 scopus 로고    scopus 로고
    • Regulation of cerebral cortical size by control of cell cycle exit in neural precursors
    • Chenn, A. and Walsh, C. A. (2002). Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science 297, 365-369.
    • (2002) Science , vol.297 , pp. 365-369
    • Chenn, A.1    Walsh, C.A.2
  • 10
    • 0028989016 scopus 로고
    • Notch1 is required for the coordinate segmentation of somites
    • Conlon, R. A., Reaume, A. G. and Rossant, J. (1995). Notch1 is required for the coordinate segmentation of somites. Development 121, 1533-1545.
    • (1995) Development , vol.121 , pp. 1533-1545
    • Conlon, R.A.1    Reaume, A.G.2    Rossant, J.3
  • 11
    • 0016206404 scopus 로고
    • Assembly of gap junctions during amphibian neurulation
    • Decker, R. S. and Friend, D. S. (1974). Assembly of gap junctions during amphibian neurulation. J. Cell Biol. 62, 32-47.
    • (1974) J. Cell Biol. , vol.62 , pp. 32-47
    • Decker, R.S.1    Friend, D.S.2
  • 12
    • 0033932628 scopus 로고    scopus 로고
    • Progressive restriction in fate potential by neural progenitors during cerebral cortical development
    • Desai, A. R. and McConnell, S. K. (2000). Progressive restriction in fate potential by neural progenitors during cerebral cortical development. Development 127, 2863-2872.
    • (2000) Development , vol.127 , pp. 2863-2872
    • Desai, A.R.1    McConnell, S.K.2
  • 13
    • 0014298195 scopus 로고
    • The germinal layer of the growing human brain during early fetal life
    • Duckett, S. (1968). The germinal layer of the growing human brain during early fetal life. Anat. Rec. 161, 231-246.
    • (1968) Anat. Rec. , vol.161 , pp. 231-246
    • Duckett, S.1
  • 14
    • 0028889751 scopus 로고
    • Mice lacking cyclin D1 are small and show defects in eye and mammary gland development
    • Fantl, V., Stamp, G., Andrews, A., Rosewell, I. and Dickson, C. (1995). Mice lacking cyclin D1 are small and show defects in eye and mammary gland development. Genes Dev. 9, 2364-2372.
    • (1995) Genes Dev. , vol.9 , pp. 2364-2372
    • Fantl, V.1    Stamp, G.2    Andrews, A.3    Rosewell, I.4    Dickson, C.5
  • 16
    • 78651165140 scopus 로고
    • Analysis of neuron differentiation in the central nervous system by tritiated thymidine autoradiography
    • Fujita, S. (1964). Analysis of neuron differentiation in the central nervous system by tritiated thymidine autoradiography. J. Comp. Neurol. 122, 311-327.
    • (1964) J. Comp. Neurol. , vol.122 , pp. 311-327
    • Fujita, S.1
  • 17
    • 0036304110 scopus 로고    scopus 로고
    • The role of Notch in promoting glial and neural stem cell fates
    • Gaiano, N. and Fishell, G. (2002). The role of Notch in promoting glial and neural stem cell fates. Annu. Rev. Neurosci. 25, 471-490.
    • (2002) Annu. Rev. Neurosci. , vol.25 , pp. 471-490
    • Gaiano, N.1    Fishell, G.2
  • 18
    • 0344447099 scopus 로고    scopus 로고
    • Blocking N-cadherin function disrupts the epithelial structure of differentiating neural tissue in the embryonic chicken brain
    • Gänzler-Ordenthal, S. I. I. and Redies, C. (1998). Blocking N-cadherin function disrupts the epithelial structure of differentiating neural tissue in the embryonic chicken brain. J. Neurosci. 18, 5415-5425.
    • (1998) J. Neurosci. , vol.18 , pp. 5415-5425
    • Gänzler-Ordenthal, S.I.I.1    Redies, C.2
  • 20
    • 0037101611 scopus 로고    scopus 로고
    • A critical function of the pial basement membrane in cortical histogenesis
    • Halfter, W., Dong, S., Yip, Y.-P., Willem, M. and Mayer, U. (2002). A critical function of the pial basement membrane in cortical histogenesis. J. Neurosci. 22, 6029-6040.
    • (2002) J. Neurosci. , vol.22 , pp. 6029-6040
    • Halfter, W.1    Dong, S.2    Yip, Y.-P.3    Willem, M.4    Mayer, U.5
  • 21
    • 0032868937 scopus 로고    scopus 로고
    • Mutation in ankyrin repeats of the mouse Notch2 gene induces early embryonic lethality
    • Hamada, Y., Kadowaki, Y., Okabe, M., Ikawa, M., Coleman, J. R. and Tsujimoto, Y. (1999). Mutation in ankyrin repeats of the mouse Notch2 gene induces early embryonic lethality. Development 126, 3415-3424.
    • (1999) Development , vol.126 , pp. 3415-3424
    • Hamada, Y.1    Kadowaki, Y.2    Okabe, M.3    Ikawa, M.4    Coleman, J.R.5    Tsujimoto, Y.6
  • 22
    • 0035035408 scopus 로고    scopus 로고
    • Roles of homeobox and bHLH genes in specification of a retinal cell type
    • Hatakeyama, J., Tomita, K., Inoue, T. and Kageyama, R. (2001). Roles of homeobox and bHLH genes in specification of a retinal cell type. Development 128, 1313-1322.
    • (2001) Development , vol.128 , pp. 1313-1322
    • Hatakeyama, J.1    Tomita, K.2    Inoue, T.3    Kageyama, R.4
  • 23
    • 0022621979 scopus 로고
    • Expression of N-cadherin adhesion molecules associated with early morphogenetic events in chick development
    • Hatta, K. and Takeichi, M. (1986). Expression of N-cadherin adhesion molecules associated with early morphogenetic events in chick development. Nature 320, 447-449.
    • (1986) Nature , vol.320 , pp. 447-449
    • Hatta, K.1    Takeichi, M.2
  • 24
    • 0032950502 scopus 로고    scopus 로고
    • Immunofluorescence detection of ezrin/radixin/moesin (ERM) proteins with their carboxyl-terminal threonine phosphorylated in cultured cells and tissues
    • Hayashi, K., Yonemura, S., Matsui, T., Tsukita, S. and Tsukita, S. (1999). Immunofluorescence detection of ezrin/radixin/moesin (ERM) proteins with their carboxyl-terminal threonine phosphorylated in cultured cells and tissues. J. Cell Sci. 112, 1149-1158.
    • (1999) J. Cell Sci. , vol.112 , pp. 1149-1158
    • Hayashi, K.1    Yonemura, S.2    Matsui, T.3    Tsukita, S.4    Tsukita, S.5
  • 25
    • 0014977557 scopus 로고
    • Cell proliferation in the neural tube: An electron microscopic and Golgi analysis in the mouse cerebral vesicle
    • Hinds, J. W. and Ruffett, T. L. (1971). Cell proliferation in the neural tube: an electron microscopic and Golgi analysis in the mouse cerebral vesicle. Z. Zellforsch. 115, 226-264.
    • (1971) Z. Zellforsch. , vol.115 , pp. 226-264
    • Hinds, J.W.1    Ruffett, T.L.2
  • 26
    • 0034705483 scopus 로고    scopus 로고
    • Generation of structurally and functionally distinct factors from the basic helix-loop-helix gene Hes3 by alternative first exons
    • Hirata, H., Ohtsuka, T., Bessho, Y. and Kageyama, R. (2000). Generation of structurally and functionally distinct factors from the basic helix-loop-helix gene Hes3 by alternative first exons. J. Biol. Chem. 275, 19083-19089.
    • (2000) J. Biol. Chem. , vol.275 , pp. 19083-19089
    • Hirata, H.1    Ohtsuka, T.2    Bessho, Y.3    Kageyama, R.4
  • 27
    • 0035882095 scopus 로고    scopus 로고
    • Hes1 and Hes3 regulate maintenance of the isthmic organizer and development of the mid/hindbrain
    • Hirata, H., Tomita, K., Bessho, Y. and Kageyama, R. (2001). Hes1 and Hes3 regulate maintenance of the isthmic organizer and development of the mid/hindbrain. EMBO J. 20, 4454-4466.
    • (2001) EMBO J. , vol.20 , pp. 4454-4466
    • Hirata, H.1    Tomita, K.2    Bessho, Y.3    Kageyama, R.4
  • 29
    • 0029678250 scopus 로고    scopus 로고
    • The shortest path from the surface to the nucleus: RBP-J κ/Su(H) transcription factor
    • Honjo, T. (1996). The shortest path from the surface to the nucleus: RBP-J κ/Su(H) transcription factor. Genes Cells 1 1-9.
    • (1996) Genes Cells , vol.1 , pp. 1-9
    • Honjo, T.1
  • 30
    • 0032966885 scopus 로고    scopus 로고
    • Cerebellar histogenesis is disturbed in mice lacking cyclin D2
    • Huard, J. M. T., Forster, C. C., Carter, M. L., Sicinski, P. and Ross, E. M. (1999). Cerebellar histogenesis is disturbed in mice lacking cyclin D2. Development 126, 1927-1935.
    • (1999) Development , vol.126 , pp. 1927-1935
    • Huard, J.M.T.1    Forster, C.C.2    Carter, M.L.3    Sicinski, P.4    Ross, E.M.5
  • 32
    • 0030727631 scopus 로고    scopus 로고
    • Helix-loop-helix factors in growth and differentiation of the vertebrate nervous system
    • Kageyama, R. and Nakanishi, S. (1997). Helix-loop-helix factors in growth and differentiation of the vertebrate nervous system. Curr. Opin. Genet. Dev. 7, 659-665.
    • (1997) Curr. Opin. Genet. Dev. , vol.7 , pp. 659-665
    • Kageyama, R.1    Nakanishi, S.2
  • 33
    • 0036208599 scopus 로고    scopus 로고
    • Differential expression patterns of Claudins, tight junction membrane proteins, in mouse nephron segments
    • Kiuchi-Saishin, Y., Gotoh, S., Furuse, M., Takasuga, A., Tano, Y. and Tsukita, S. (2002). Differential expression patterns of Claudins, tight junction membrane proteins, in mouse nephron segments. J. Am. Soc. Nephrol. 13, 875-886.
    • (2002) J. Am. Soc. Nephrol. , vol.13 , pp. 875-886
    • Kiuchi-Saishin, Y.1    Gotoh, S.2    Furuse, M.3    Takasuga, A.4    Tano, Y.5    Tsukita, S.6
  • 34
    • 0026623402 scopus 로고
    • Immunohistochemical and biochemical analysis of N-cadherin expression during CNS development
    • Lagunowich, L. A., Schneider, J. C., Chasen, S. and Grunwald, G. B. (1992). Immunohistochemical and biochemical analysis of N-cadherin expression during CNS development. J. Neurosci. Res. 32, 202-208.
    • (1992) J. Neurosci. Res. , vol.32 , pp. 202-208
    • Lagunowich, L.A.1    Schneider, J.C.2    Chasen, S.3    Grunwald, G.B.4
  • 36
    • 0022069874 scopus 로고
    • Do neurons in the vertebrate CNS migrate on laminin?
    • Liesi, P. (1985). Do neurons in the vertebrate CNS migrate on laminin? EMBO J. 4, 1163-1170.
    • (1985) EMBO J. , vol.4 , pp. 1163-1170
    • Liesi, P.1
  • 39
    • 0031001710 scopus 로고    scopus 로고
    • The Rx homeobox gene is essential for vertebrate eye development
    • Mathers, P. H., Grinberg, A., Mahon, K. A. and Jamrich, M. (1997). The Rx homeobox gene is essential for vertebrate eye development. Nature 387, 603-607.
    • (1997) Nature , vol.387 , pp. 603-607
    • Mathers, P.H.1    Grinberg, A.2    Mahon, K.A.3    Jamrich, M.4
  • 40
    • 0028858680 scopus 로고
    • Constructing the cerebral cortex: Neurogenesis and fate determination
    • McConnell, S. K. (1995). Constructing the cerebral cortex: neurogenesis and fate determination. Neuron 15, 761-768.
    • (1995) Neuron , vol.15 , pp. 761-768
    • McConnell, S.K.1
  • 41
    • 0023229532 scopus 로고
    • Cell junctions and membrane specializations in the ventricular zone (germinal matrix) of the developing sheep brain: A CSF-brain barrier
    • Møllgård, K., Balslev, Y., Lauritzen, B. and Saunders, N. R. (1987). Cell junctions and membrane specializations in the ventricular zone (germinal matrix) of the developing sheep brain: a CSF-brain barrier. J. Neurocytol. 16, 433-444.
    • (1987) J. Neurocytol. , vol.16 , pp. 433-444
    • Møllgård, K.1    Balslev, Y.2    Lauritzen, B.3    Saunders, N.R.4
  • 44
    • 0141918786 scopus 로고    scopus 로고
    • Neurogenesis and the cell cycle
    • Ohnuma, S. and Harris, W. A. (2003). Neurogenesis and the cell cycle. Neuron 40, 199-208.
    • (2003) Neuron , vol.40 , pp. 199-208
    • Ohnuma, S.1    Harris, W.A.2
  • 46
    • 0035839458 scopus 로고    scopus 로고
    • Roles of the basic helix-loop-helix genes Hes1 and Hes5 in expansion of neural stem cells of the developing brain
    • Ohtsuka, T., Sakamoto, M., Guillemot, F. and 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, 30467-30474.
    • (2001) J. Biol. Chem. , vol.276 , pp. 30467-30474
    • Ohtsuka, T.1    Sakamoto, M.2    Guillemot, F.3    Kageyama, R.4
  • 47
    • 0033636521 scopus 로고    scopus 로고
    • Timing of CNS cell generation: A programmed sequence of neuron and glial cell production from isolated murine cortical stem cells
    • Qian, X., Shen, Q., Goderie, S. K., He, W., Capela, A., Davis, A. A. and Temple, S. (2000). Timing of CNS cell generation: a programmed sequence of neuron and glial cell production from isolated murine cortical stem cells. Neuron 28, 69-80.
    • (2000) Neuron , vol.28 , pp. 69-80
    • Qian, X.1    Shen, Q.2    Goderie, S.K.3    He, W.4    Capela, A.5    Davis, A.A.6    Temple, S.7
  • 48
    • 0027288524 scopus 로고
    • Differential expression of N- and R-cadherin in functional neuronal systems and other structures of the developing chicken brain
    • Redies, C., Engelhart, K. and Takeichi, M. (1993). Differential expression of N- and R-cadherin in functional neuronal systems and other structures of the developing chicken brain. J. Comp. Neurol. 333, 398-416.
    • (1993) J. Comp. Neurol. , vol.333 , pp. 398-416
    • Redies, C.1    Engelhart, K.2    Takeichi, M.3
  • 49
    • 0016583535 scopus 로고
    • Cell junctions in development, with particular reference to the neural tube
    • Revel, J.-P. and Brown, S. S. (1975). Cell junctions in development, with particular reference to the neural tube. Cold Spring Harbor Symp. Quant. Biol. 40, 443-455.
    • (1975) Cold Spring Harbor Symp. Quant. Biol. , vol.40 , pp. 443-455
    • Revel, J.-P.1    Brown, S.S.2
  • 50
    • 0041355557 scopus 로고    scopus 로고
    • Notch and presenilin: Regulated intramembrane proteolysis links development and degeneration
    • Selkoe, D. and Kopan, R. (2003). Notch and presenilin: regulated intramembrane proteolysis links development and degeneration. Annu. Rev. Neurosci. 26, 565-597.
    • (2003) Annu. Rev. Neurosci. , vol.26 , pp. 565-597
    • Selkoe, D.1    Kopan, R.2
  • 55
    • 0035499887 scopus 로고    scopus 로고
    • The development of neural stem cells
    • Temple, S. (2001). The development of neural stem cells. Nature 414, 112-117.
    • (2001) Nature , vol.414 , pp. 112-117
    • Temple, S.1
  • 56
    • 0027279422 scopus 로고
    • Genes coding for basement membrane glycoproteins laminin, nidogen, and collagen IV are differentially expressed in the nervous system and by epithelial, endothelial, and mesenchymal cells of the mouse embryo
    • Thomas, T. and Dziadek, M. (1993). Genes coding for basement membrane glycoproteins laminin, nidogen, and collagen IV are differentially expressed in the nervous system and by epithelial, endothelial, and mesenchymal cells of the mouse embryo. Exp. Cell Res. 208, 54-67.
    • (1993) Exp. Cell Res. , vol.208 , pp. 54-67
    • Thomas, T.1    Dziadek, M.2
  • 57
    • 0030271572 scopus 로고    scopus 로고
    • Macromolecular organization of basement membranes
    • Timpl, R. (1996). Macromolecular organization of basement membranes. Curr. Opin. Cell Biol. 8, 618-624.
    • (1996) Curr. Opin. Cell Biol. , vol.8 , pp. 618-624
    • Timpl, R.1
  • 58
    • 0029977614 scopus 로고    scopus 로고
    • Mammalian hairy and Enhancer of split homolog 1 regulates differentiation of retinal neurons and is essential for eye morphogenesis
    • Tomita, K., Ishibashi, M., Nakahara, K., Ang, S.-L., Nakanishi, S., Guillemot, F. and Kageyama, R. (1996). Mammalian hairy and Enhancer of split homolog 1 regulates differentiation of retinal neurons and is essential for eye morphogenesis. Neuron 16, 723-734.
    • (1996) Neuron , vol.16 , pp. 723-734
    • Tomita, K.1    Ishibashi, M.2    Nakahara, K.3    Ang, S.-L.4    Nakanishi, S.5    Guillemot, F.6    Kageyama, R.7
  • 59
    • 0029953417 scopus 로고    scopus 로고
    • Pax2 contributes to inner ear patterning and optic nerve trajectory
    • Torres, M., Gómez-Pardo, E. and Gruss, P. (1996). Pax2 contributes to inner ear patterning and optic nerve trajectory. Development 122, 3381-3391.
    • (1996) Development , vol.122 , pp. 3381-3391
    • Torres, M.1    Gómez-Pardo, E.2    Gruss, P.3
  • 61
    • 0018167496 scopus 로고
    • One molecule of diphtheria toxin fragment A introduced into a cell can kill the cell
    • Yamaizumi, M., Mekada, E., Uchida, T. and Okada, Y. (1978). One molecule of diphtheria toxin fragment A introduced into a cell can kill the cell. Cell 15, 245-250.
    • (1978) Cell , vol.15 , pp. 245-250
    • Yamaizumi, M.1    Mekada, E.2    Uchida, T.3    Okada, Y.4
  • 63
    • 0028057681 scopus 로고
    • Independent regulatory elements in the nestin gene direct transgene expression to neural stem cells or muscle precursors
    • Zimmerman, L., Lendahl, U., Cunningham, M., Mckay, R., Parr, B., Gavin, B., Mann, J., Vassileva, G. and McMahon, A. (1994). Independent regulatory elements in the nestin gene direct transgene expression to neural stem cells or muscle precursors. Neuron 12 11-24.
    • (1994) Neuron , vol.12 , pp. 11-24
    • Zimmerman, L.1    Lendahl, U.2    Cunningham, M.3    McKay, R.4    Parr, B.5    Gavin, B.6    Mann, J.7    Vassileva, G.8    McMahon, A.9


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.