title: Neural stem/progenitor cells derived from the embryonic dorsal telencephalon of D6/GFP mice differentiate primarily into neurons after transplantation into a cortical lesion.
abstract: D6 is a promoter/enhancer of the mDach1 gene that is involved in the development of the neocortex and hippocampus. It is expressed by proliferating neural stem/progenitor cells (NSPCs) of the cortex at early stages of neurogenesis. The differentiation potential of NSPCs isolated from embryonic day 12 mouse embryos, in which the expression of green fluorescent protein (GFP) is driven by the D6 promoter/enhancer, has been studied in vitro and after transplantation into the intact adult rat brain as well as into the site of a photochemical lesion. The electrophysiological properties of D6/GFP-derived cells were studied using the whole-cell patch-clamp technique, and immunohistochemical analyses were carried out. D6/GFP-derived neurospheres expressed markers of radial glia and gave rise predominantly to immature neurons and GFAP-positive cells during in vitro differentiation. One week after transplantation into the intact brain or into the site of a photochemical lesion, transplanted cells expressed only neuronal markers. D6/GFP-derived neurons were characterised by the expression of tetrodotoxin-sensitive Na(+)-currents and K (A)- and K (DR) currents sensitive to 4-aminopyridine. They were able to fire repetitive action potentials and responded to the application of GABA. Our results indicate that after transplantation into the site of a photochemical lesion, D6/GFP-derived NSPCs survive and differentiate into neurons, and their membrane properties are comparable to those transplanted into the non-injured cortex. Therefore, region-specific D6/GFP-derived NSPCs represent a promising tool for studying neurogenesis and cell replacement in a damaged cellular environment.
authors.affiliation: Laboratory of Neurobiology, Department of Cellular Neurophysiology, Institute of Experimental Medicine ASCR v.v.i., Videnska 1083, 142 20, Prague 4, Czech Republic.
authors.forename: Iva
authors.initials: I
authors.lastname: Prajerova
authors.forename: Pavel
authors.initials: P
authors.lastname: Honsa
authors.forename: Alexandr
authors.initials: A
authors.lastname: Chvatal
authors.forename: Miroslava
authors.initials: M
authors.lastname: Anderova
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D018756:GABA Antagonists / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D013687:Telencephalon / Q000166:cytology / Q000473:pathology / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018756:GABA Antagonists; D026902:Potassium Channel Blockers; D011993:Recombinant Fusion Proteins; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline
references.citation: J Neurosci. 1996 Feb 1;16(3):1131-9
references.pmid: 8558242
references.citation: Mol Cell Neurosci. 2006 May-Jun;32(1-2):15-26
references.pmid: 16530423
references.citation: Eur J Neurosci. 2007 Feb;25(3):635-48
references.pmid: 17313568
references.citation: Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17172-7
references.pmid: 16284248
references.citation: J Neurosci. 2007 Apr 18;27(16):4233-42
references.pmid: 17442807
references.citation: Neuron. 2000 Oct;28(1):69-80
references.pmid: 11086984
references.citation: Brain. 2006 Dec;129(Pt 12):3238-48
references.pmid: 17018551
references.citation: J Neurosci. 2007 Mar 21;27(12):3069-77
references.pmid: 17376968
references.citation: Eur J Neurosci. 2007 Aug;26(3):605-14
references.pmid: 17686040
references.citation: Glia. 2006 Oct;54(5):394-410
references.pmid: 16886203
references.citation: PLoS One. 2008 Feb 13;3(2):e1604
references.pmid: 18270591
references.citation: J Neurosci. 2008 May 21;28(21):5547-58
references.pmid: 18495889
references.citation: J Neurosci Res. 2006 Aug 15;84(3):471-82
references.pmid: 16721767
references.citation: J Neurosci. 2007 Apr 4;27(14):3875-83
references.pmid: 17409252
references.citation: Development. 2005 Oct;132(20):4497-508
references.pmid: 16162650
references.citation: J Neurophysiol. 2000 Jan;83(1):70-80
references.pmid: 10634854
references.citation: Nature. 2001 Feb 8;409(6821):714-20
references.pmid: 11217860
references.citation: Biochem J. 2004 Jul 15;381(Pt 2):471-81
references.pmid: 15099191
references.citation: Mol Cell Neurosci. 2005 Nov;30(3):388-97
references.pmid: 16150605
references.citation: J Neurosci Res. 2007 Jun;85(8):1606-17
references.pmid: 17455290
references.citation: Regen Med. 2007 Nov;2(6):929-45
references.pmid: 18034631
references.citation: PLoS One. 2008 Sep 11;3(9):e3189
references.pmid: 18784832
references.citation: Glia. 2009 Jan 1;57(1):39-53
references.pmid: 18661555
references.citation: J Neurosurg. 2007 Jul;107(1):145-54
references.pmid: 17639884
references.citation: Stem Cells. 2007 Feb;25(2):340-53
references.pmid: 17053213
references.citation: Eur J Neurosci. 2007 Feb;25(4):1006-22
references.pmid: 17331197
references.citation: Hippocampus. 2007;17(11):1037-48
references.pmid: 17604346
references.citation: Exp Neurol. 2003 Dec;184(2):615-35
references.pmid: 14769354
references.citation: J Neurophysiol. 2006 Jan;95(1):134-43
references.pmid: 16093329
references.citation: J Physiol. 2000 Jun 15;525 Pt 3:621-39
references.pmid: 10856117
references.citation: Brain Res. 2006 May 17;1089(1):79-91
references.pmid: 16643860
references.citation: Nat Neurosci. 2003 Dec;6(12):1277-83
references.pmid: 14625554
references.citation: J Neurophysiol. 2003 Apr;89(4):1761-73
references.pmid: 12611962
references.citation: Neuroscience. 2002;112(4):951-66
references.pmid: 12088753
references.citation: Mol Cell Neurosci. 2008 Feb;37(2):284-97
references.pmid: 18023363
references.citation: J Neurosci Res. 2006 Jun;83(8):1494-501
references.pmid: 16547970
references.citation: Genes Dev. 2005 May 1;19(9):1028-33
references.pmid: 15879553
references.citation: Eur J Neurosci. 2004 May;19(9):2475-87
references.pmid: 15128401
references.citation: Ann Neurol. 1985 May;17(5):497-504
references.pmid: 4004172
references.citation: J Neurocytol. 2004 May;33(3):309-19
references.pmid: 15475686
references.citation: Brain Res. 2002 Dec 20;958(1):70-82
references.pmid: 12468031
references.citation: J Neurosci. 2007 Apr 11;27(15):4132-45
references.pmid: 17428991
references.citation: Neuron. 2003 Oct 30;40(3):485-99
references.pmid: 14642274
references.citation: J Neurobiol. 2006 Sep 1;66(10):1084-100
references.pmid: 16838369
references.citation: J Neurophysiol. 1999 Aug;82(2):570-83
references.pmid: 10444657
references.citation: Prog Brain Res. 2002;136:73-80
references.pmid: 12143405
references.citation: Nature. 2006 Feb 2;439(7076):589-93
references.pmid: 16341203
references.citation: Exp Neurol. 2002 Jan;173(1):1-21
references.pmid: 11771935
references.citation: J Neurosci Res. 2006 Dec;84(8):1630-44
references.pmid: 17044030
references.citation: Development. 2000 Dec;127(24):5253-63
references.pmid: 11076748
references.citation: J Neurosci Methods. 1994 Jan;51(1):107-16
references.pmid: 8189746
references.citation: Neurosci Lett. 2007 May 23;419(1):49-54
references.pmid: 17420097
references.citation: Exp Neurol. 2006 May;199(1):222-35
references.pmid: 16714017
references.citation: J Physiol. 2004 Jun 15;557(Pt 3):829-41
references.pmid: 15090604
references.citation: Neuron. 2004 Jan 22;41(2):215-27
references.pmid: 14741103
references.citation: J Neurosci Res. 2004 Jun 15;76(6):801-11
references.pmid: 15160392
references.citation: J Neurosci. 1998 Oct 15;18(20):8111-25
references.pmid: 9763458
references.citation: Nature. 2008 Sep 18;455(7211):351-7
references.pmid: 18716623
references.citation: Mol Cell Neurosci. 2003 Aug;23(4):531-43
references.pmid: 12932435
references.citation: J Neurosci. 1994 Mar;14(3 Pt 1):1030-7
references.pmid: 8120611
references.citation: Pflugers Arch. 2007 Mar;453(6):839-49
references.pmid: 17031668
references.citation: Neurosci Lett. 2007 Jun 8;420(1):23-8
references.pmid: 17499438
references.citation: Development. 2005 Aug;132(15):3345-56
references.pmid: 16014513
references.citation: Pflugers Arch. 1981 Aug;391(2):85-100
references.pmid: 6270629
references.citation: Cereb Cortex. 2007 Jan;17(1):138-48
references.pmid: 16452638
references.citation: Neurosci Res. 2001 Sep;41(1):51-60
references.pmid: 11535293
references.citation: Glia. 2004 Dec;48(4):311-26
references.pmid: 15390116
references.citation: Eur J Neurosci. 2002 Jul;16(2):197-208
references.pmid: 12169102
references.citation: Int J Clin Exp Med. 2008;1(2):145-53
references.pmid: 19079668
references.citation: Dev Biol. 2001 Jan 1;229(1):15-30
references.pmid: 11133151
references.citation: Cell Stem Cell. 2008 Nov 6;3(5):519-32
references.pmid: 18983967
references.citation: Neuroscience. 2008 Aug 26;155(3):760-70
references.pmid: 18588947
references.citation: J Neurosci Res. 2006 Apr;83(5):731-43
references.pmid: 16496354
references.citation: Eur J Neurosci. 2003 Apr;17(7):1375-83
references.pmid: 12713640
references.citation: Dev Biol. 2008 Aug 15;320(2):456-68
references.pmid: 18582453
references.citation: Exp Cell Res. 2003 Oct 1;289(2):378-83
references.pmid: 14499639
references.citation: Mol Cell Neurosci. 2004 Apr;25(4):664-78
references.pmid: 15080895
references.citation: Cell Transplant. 2008;17(7):735-51
references.pmid: 19044201
references.citation: J Neurosci. 1997 Jan 1;17(1):58-69
references.pmid: 8987736
references.citation: J Neurosci. 2002 Dec 1;22(23):10106-15
references.pmid: 12451111
references.citation: Neuroscience. 2006 May 12;139(2):513-30
references.pmid: 16458439
references.citation: J Neurophysiol. 2000 Jul;84(1):534-48
references.pmid: 10899225
references.citation: Stem Cells. 2005 Aug;23(7):931-45
references.pmid: 16043459
references.citation: Neuron. 2003 Mar 6;37(5):751-64
references.pmid: 12628166
references.citation: J Neurosci. 1994 Sep;14(9):5399-416
references.pmid: 8083744
references.citation: Glia. 2005 Dec;52(4):289-300
references.pmid: 16001427
references.citation: J Neurosci. 2007 May 9;27(19):5224-35
references.pmid: 17494709
references.citation: Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13366-71
references.pmid: 11087876
references.citation: Physiol Behav. 2007 Sep 10;92(1-2):60-6
references.pmid: 17610915
references.citation: Exp Neurol. 2007 Jan;203(1):128-36
references.pmid: 17010971
references.citation: Neuron. 1995 Dec;15(6):1287-98
references.pmid: 8845153