Neural stem/progenitor cells derived from the embryonic dorsal telencephalon of D6/GFP mice differentiate primarily into neurons after transplantation into a cortical lesion.
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.
Prajerova
Iva
I
Laboratory of Neurobiology, Department of Cellular Neurophysiology, Institute of Experimental Medicine ASCR v.v.i., Videnska 1083, 142 20, Prague 4, Czech Republic.
Honsa
Pavel
P
Chvatal
Alexandr
A
Anderova
Miroslava
M
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
D015415:Biomarkers; D018756:GABA Antagonists; D026902:Potassium Channel Blockers; D011993:Recombinant Fusion Proteins; D005680:gamma-Aminobutyric Acid; D001640:Bicuculline
J Neurosci. 1996 Feb 1;16(3):1131-9
8558242
Mol Cell Neurosci. 2006 May-Jun;32(1-2):15-26
16530423
Eur J Neurosci. 2007 Feb;25(3):635-48
17313568
Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17172-7
16284248
J Neurosci. 2007 Apr 18;27(16):4233-42
17442807
Neuron. 2000 Oct;28(1):69-80
11086984
Brain. 2006 Dec;129(Pt 12):3238-48
17018551
J Neurosci. 2007 Mar 21;27(12):3069-77
17376968
Eur J Neurosci. 2007 Aug;26(3):605-14
17686040
Glia. 2006 Oct;54(5):394-410
16886203
PLoS One. 2008 Feb 13;3(2):e1604
18270591
J Neurosci. 2008 May 21;28(21):5547-58
18495889
J Neurosci Res. 2006 Aug 15;84(3):471-82
16721767
J Neurosci. 2007 Apr 4;27(14):3875-83
17409252
Development. 2005 Oct;132(20):4497-508
16162650
J Neurophysiol. 2000 Jan;83(1):70-80
10634854
Nature. 2001 Feb 8;409(6821):714-20
11217860
Biochem J. 2004 Jul 15;381(Pt 2):471-81
15099191
Mol Cell Neurosci. 2005 Nov;30(3):388-97
16150605
J Neurosci Res. 2007 Jun;85(8):1606-17
17455290
Regen Med. 2007 Nov;2(6):929-45
18034631
PLoS One. 2008 Sep 11;3(9):e3189
18784832
Glia. 2009 Jan 1;57(1):39-53
18661555
J Neurosurg. 2007 Jul;107(1):145-54
17639884
Stem Cells. 2007 Feb;25(2):340-53
17053213
Eur J Neurosci. 2007 Feb;25(4):1006-22
17331197
Hippocampus. 2007;17(11):1037-48
17604346
Exp Neurol. 2003 Dec;184(2):615-35
14769354
J Neurophysiol. 2006 Jan;95(1):134-43
16093329
J Physiol. 2000 Jun 15;525 Pt 3:621-39
10856117
Brain Res. 2006 May 17;1089(1):79-91
16643860
Nat Neurosci. 2003 Dec;6(12):1277-83
14625554
J Neurophysiol. 2003 Apr;89(4):1761-73
12611962
Neuroscience. 2002;112(4):951-66
12088753
Mol Cell Neurosci. 2008 Feb;37(2):284-97
18023363
J Neurosci Res. 2006 Jun;83(8):1494-501
16547970
Genes Dev. 2005 May 1;19(9):1028-33
15879553
Eur J Neurosci. 2004 May;19(9):2475-87
15128401
Ann Neurol. 1985 May;17(5):497-504
4004172
J Neurocytol. 2004 May;33(3):309-19
15475686
Brain Res. 2002 Dec 20;958(1):70-82
12468031
J Neurosci. 2007 Apr 11;27(15):4132-45
17428991
Neuron. 2003 Oct 30;40(3):485-99
14642274
J Neurobiol. 2006 Sep 1;66(10):1084-100
16838369
J Neurophysiol. 1999 Aug;82(2):570-83
10444657
Prog Brain Res. 2002;136:73-80
12143405
Nature. 2006 Feb 2;439(7076):589-93
16341203
Exp Neurol. 2002 Jan;173(1):1-21
11771935
J Neurosci Res. 2006 Dec;84(8):1630-44
17044030
Development. 2000 Dec;127(24):5253-63
11076748
J Neurosci Methods. 1994 Jan;51(1):107-16
8189746
Neurosci Lett. 2007 May 23;419(1):49-54
17420097
Exp Neurol. 2006 May;199(1):222-35
16714017
J Physiol. 2004 Jun 15;557(Pt 3):829-41
15090604
Neuron. 2004 Jan 22;41(2):215-27
14741103
J Neurosci Res. 2004 Jun 15;76(6):801-11
15160392
J Neurosci. 1998 Oct 15;18(20):8111-25
9763458
Nature. 2008 Sep 18;455(7211):351-7
18716623
Mol Cell Neurosci. 2003 Aug;23(4):531-43
12932435
J Neurosci. 1994 Mar;14(3 Pt 1):1030-7
8120611
Pflugers Arch. 2007 Mar;453(6):839-49
17031668
Neurosci Lett. 2007 Jun 8;420(1):23-8
17499438
Development. 2005 Aug;132(15):3345-56
16014513
Pflugers Arch. 1981 Aug;391(2):85-100
6270629
Cereb Cortex. 2007 Jan;17(1):138-48
16452638
Neurosci Res. 2001 Sep;41(1):51-60
11535293
Glia. 2004 Dec;48(4):311-26
15390116
Eur J Neurosci. 2002 Jul;16(2):197-208
12169102
Int J Clin Exp Med. 2008;1(2):145-53
19079668
Dev Biol. 2001 Jan 1;229(1):15-30
11133151
Cell Stem Cell. 2008 Nov 6;3(5):519-32
18983967
Neuroscience. 2008 Aug 26;155(3):760-70
18588947
J Neurosci Res. 2006 Apr;83(5):731-43
16496354
Eur J Neurosci. 2003 Apr;17(7):1375-83
12713640
Dev Biol. 2008 Aug 15;320(2):456-68
18582453
Exp Cell Res. 2003 Oct 1;289(2):378-83
14499639
Mol Cell Neurosci. 2004 Apr;25(4):664-78
15080895
Cell Transplant. 2008;17(7):735-51
19044201
J Neurosci. 1997 Jan 1;17(1):58-69
8987736
J Neurosci. 2002 Dec 1;22(23):10106-15
12451111
Neuroscience. 2006 May 12;139(2):513-30
16458439
J Neurophysiol. 2000 Jul;84(1):534-48
10899225
Stem Cells. 2005 Aug;23(7):931-45
16043459
Neuron. 2003 Mar 6;37(5):751-64
12628166
J Neurosci. 1994 Sep;14(9):5399-416
8083744
Glia. 2005 Dec;52(4):289-300
16001427
J Neurosci. 2007 May 9;27(19):5224-35
17494709
Proc Natl Acad Sci U S A. 2000 Nov 21;97(24):13366-71
11087876
Physiol Behav. 2007 Sep 10;92(1-2):60-6
17610915
Exp Neurol. 2007 Jan;203(1):128-36
17010971
Neuron. 1995 Dec;15(6):1287-98
8845153