title: The integrity of cholinergic basal forebrain neurons depends on expression of Nkx2-1.
abstract: The transcription factor Nkx2-1 belongs to the homeobox-encoding family of proteins that have essential functions in prenatal brain development. Nkx2-1 is required for the specification of cortical interneurons and several neuronal subtypes of the ventral forebrain. Moreover, this transcription factor is involved in migratory processes by regulating the expression of guidance molecules. Interestingly, Nkx2-1 expression was recently detected in the mouse brain at postnatal stages. Using two transgenic mouse lines that allow prenatal or postnatal cell type-specific deletion of Nkx2-1, we show that continuous expression of the transcription factor is essential for the maturation and maintenance of cholinergic basal forebrain neurons in mice. Notably, prenatal deletion of Nkx2-1 in GAD67-expressing neurons leads to a nearly complete loss of cholinergic neurons and parvalbumin-containing GABAergic neurons in the basal forebrain. We also show that postnatal mutation of Nkx2-1 in choline acetyltransferase-expressing cells causes a striking reduction in their number. These degenerative changes are accompanied by partial denervation of their target structures and results in a discrete impairment of spatial memory.
authors.affiliation: Institute of Cell Biology and Neurobiology, Centre of Anatomy, Charité Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Magno
authors.forename: Oliver
authors.initials: O
authors.lastname: Kretz
authors.forename: Bettina
authors.initials: B
authors.lastname: Bert
authors.forename: Sara
authors.initials: S
authors.lastname: Ersözlü
authors.forename: Johannes
authors.initials: J
authors.lastname: Vogt
authors.forename: Heidrun
authors.initials: H
authors.lastname: Fink
authors.forename: Shioko
authors.initials: S
authors.lastname: Kimura
authors.forename: Angelika
authors.initials: A
authors.lastname: Vogt
authors.forename: Hannah
authors.initials: H
authors.lastname: Monyer
authors.forename: Robert
authors.initials: R
authors.lastname: Nitsch
authors.forename: Thomas
authors.initials: T
authors.lastname: Naumann
mesh_terms: D000328:Adult; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D059329:Cholinergic Neurons / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D059330:GABAergic Neurons / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D018782:Maze Learning; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010320:Parvalbumins / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology* / Q000473:pathology / Q000502:physiology; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; D010320:Parvalbumins; D017475:Receptors, Nerve Growth Factor; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1
references.citation: J Neurosci. 2007 Sep 5;27(36):9682-95
references.pmid: 17804629
references.citation: Brain Res. 1989 Jan 30;478(2):375-81
references.pmid: 2924136
references.citation: Genes Dev. 1996 Jan 1;10(1):60-9
references.pmid: 8557195
references.citation: Eur J Neurosci. 2005 Jun;21(11):2923-38
references.pmid: 15978004
references.citation: Front Neuroanat. 2011 Feb 07;5:6
references.pmid: 21344017
references.citation: Development. 2009 Nov;136(22):3841-51
references.pmid: 19855026
references.citation: J Neurosci. 1996 Jun 15;16(12):3991-4004
references.pmid: 8656293
references.citation: J Comp Neurol. 1994 Dec 22;350(4):587-611
references.pmid: 7890832
references.citation: J Comp Neurol. 1997 Mar 24;379(4):467-81
references.pmid: 9067837
references.citation: Biochem Biophys Res Commun. 2006 Oct 27;349(3):969-75
references.pmid: 16970909
references.citation: Neuron. 2008 Sep 11;59(5):722-32
references.pmid: 18786356
references.citation: Brain Res. 2009 Dec 22;1304:164-86
references.pmid: 19766601
references.citation: Brain Res. 1987 May 19;411(2):310-31
references.pmid: 3607436
references.citation: Proc Natl Acad Sci U S A. 2005 Jul 19;102(29):10357-62
references.pmid: 16002470
references.citation: Trends Neurosci. 1995 Jul;18(7):321-6
references.pmid: 7571013
references.citation: Neuroscience. 2009 Feb 18;158(4):1224-33
references.pmid: 19095044
references.citation: Anat Rec. 1991 Dec;231(4):482-97
references.pmid: 1793176
references.citation: Brain Res. 1983 Jul;285(1):45-52
references.pmid: 6136314
references.citation: Hum Mol Genet. 2002 Apr 15;11(8):971-9
references.pmid: 11971878
references.citation: Dev Biol. 1994 Sep;165(1):243-56
references.pmid: 8088442
references.citation: J Comp Neurol. 2008 Jan 1;506(1):16-29
references.pmid: 17990269
references.citation: Exp Neurol. 2003 Jul;182(1):103-12
references.pmid: 12821380
references.citation: J Comp Neurol. 1983 Feb 20;214(2):170-97
references.pmid: 6841683
references.citation: Annu Rev Neurosci. 2001;24:1217-81
references.pmid: 11520933
references.citation: Neurobiol Learn Mem. 2005 Jul;84(1):57-68
references.pmid: 15936683
references.citation: Trends Neurosci. 2000 Mar;23(3):120-6
references.pmid: 10675916
references.citation: Hippocampus. 1996;6(5):535-45
references.pmid: 8953306
references.citation: J Comp Neurol. 1992 Nov 8;325(2):219-42
references.pmid: 1460114
references.citation: J Neurobiol. 1998 Dec;37(4):582-94
references.pmid: 9858260
references.citation: Neuron. 2005 Nov 23;48(4):591-604
references.pmid: 16301176
references.citation: J Comp Neurol. 1996 Aug 19;372(2):204-14
references.pmid: 8863126
references.citation: Clin Genet. 2008 Mar;73(3):212-26
references.pmid: 18241223
references.citation: Neurobiol Learn Mem. 2002 Jul;78(1):11-22
references.pmid: 12071664
references.citation: Brain Res. 1986 Jul;387(1):53-62
references.pmid: 3742234
references.citation: J Neurosci. 2002 Apr 1;22(7):2409-18
references.pmid: 11923404
references.citation: J Comp Neurol. 1995 Nov 20;362(3):385-99
references.pmid: 8576446
references.citation: J Neurosci. 1995 Apr;15(4):2888-905
references.pmid: 7536822
references.citation: J Neurosci. 2010 Feb 24;30(8):2824-34
references.pmid: 20181580
references.citation: J Comp Neurol. 1998 Jan 26;390(4):481-96
references.pmid: 9450531
references.citation: Acta Neuropathol. 1987;75(2):140-6
references.pmid: 3434221
references.citation: Genes Dev. 2000 Dec 1;14(23):2919-37
references.pmid: 11114882
references.citation: J Clin Invest. 2002 Feb;109(4):469-73
references.pmid: 11854318
references.citation: Biochem Pharmacol. 2005 Oct 15;70(8):1115-24
references.pmid: 15975560
references.citation: Science. 1995 Oct 27;270(5236):593-8
references.pmid: 7570017
references.citation: J Neurosci. 1993 Jul;13(7):2739-48
references.pmid: 8331370
references.citation: Mol Endocrinol. 2006 Aug;20(8):1796-809
references.pmid: 16601074
references.citation: J Neurosci. 2000 Aug 15;20(16):6063-76
references.pmid: 10934256
references.citation: J Clin Invest. 2002 Feb;109(4):475-80
references.pmid: 11854319
references.citation: J Comp Neurol. 2008 Jan 1;506(1):46-74
references.pmid: 17990271
references.citation: Mov Disord. 2007 Dec;22(16):2297-305; quiz 2452
references.pmid: 17702033
references.citation: J Neurosci. 1998 May 1;18(9):3273-81
references.pmid: 9547236
references.citation: Neurosci Biobehav Rev. 2003 Sep;27(4):401-11
references.pmid: 12946692
references.citation: Annu Rev Neurosci. 1999;22:295-318
references.pmid: 10202541
references.citation: Philos Trans R Soc Lond B Biol Sci. 2006 Sep 29;361(1473):1545-64
references.pmid: 16939974
references.citation: J Comp Neurol. 1992 Nov 8;325(2):207-18
references.pmid: 1281173
references.citation: Curr Opin Neurobiol. 2002 Feb;12(1):26-34
references.pmid: 11861161
references.citation: J Neurosci. 2010 Feb 24;30(8):2812-23
references.pmid: 20181579
references.citation: Development. 2008 Apr;135(8):1559-67
references.pmid: 18339674
references.citation: J Comp Neurol. 1979 Jan 1;183(1):89-106
references.pmid: 758337
references.citation: J Biol Chem. 2003 Jul 18;278(29):27043-52
references.pmid: 12730191
references.citation: J Comp Neurol. 2000 Aug 28;424(3):409-38
references.pmid: 10906711
references.citation: Development. 1999 Aug;126(15):3359-70
references.pmid: 10393115
references.citation: Neurogenetics. 2005 Dec;6(4):209-15
references.pmid: 16220345
references.citation: J Comp Neurol. 2000 Sep 4;424(4):607-27
references.pmid: 10931484
references.citation: J Neurosci. 1983 Nov;3(11):2286-91
references.pmid: 6355402
references.citation: J Comp Neurol. 1997 Jun 30;383(2):163-77
references.pmid: 9182846
references.citation: Neuron. 2008 Sep 11;59(5):733-45
references.pmid: 18786357
references.citation: J Neurosci. 2006 Dec 20;26(51):13167-79
references.pmid: 17182767