title: The early fetal development of human neocortical GABAergic interneurons.
abstract: GABAergic interneurons are crucial to controlling the excitability and responsiveness of cortical circuitry. Their developmental origin may differ between rodents and human. We have demonstrated the expression of 12 GABAergic interneuron-associated genes in samples from human neocortex by quantitative rtPCR from 8 to 12 postconceptional weeks (PCW) and shown a significant anterior to posterior expression gradient, confirmed by in situ hybridization or immunohistochemistry for GAD1 and 2, DLX1, 2, and 5, ASCL1, OLIG2, and CALB2. Following cortical plate (CP) formation from 8 to 9 PCW, a proportion of cells were strongly stained for all these markers in the CP and presubplate. ASCL1 and DLX2 maintained high expression in the proliferative zones and showed extensive immunofluorescent double-labeling with the cell division marker Ki-67. CALB2-positive cells increased steadily in the SVZ/VZ from 10 PCW but were not double-labeled with Ki-67. Expression of GABAergic genes was generally higher in the dorsal pallium than in the ganglionic eminences, with lower expression in the intervening ventral pallium. It is widely accepted that the cortical proliferative zones may generate CALB2-positive interneurons from mid-gestation; we now show that the anterior neocortical proliferative layers especially may be a rich source of interneurons in the early neocortex.
authors.affiliation: Institute of Neuroscience Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK.
authors.forename: Nahidh
authors.initials: N
authors.lastname: Al-Jaberi
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Lindsay
authors.affiliation: Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK.
authors.forename: Subrot
authors.initials: S
authors.lastname: Sarma
authors.affiliation: Institute of Neuroscience Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK Current address: Sheffield Institute for Translational Neuroscience (SITraN), Department of Neuroscience, University of Sheffield, Sheffield S10 2HQ, UK.
authors.forename: Nadhim
authors.initials: N
authors.lastname: Bayatti
authors.affiliation: Institute of Neuroscience.
authors.forename: Gavin J
authors.initials: GJ
authors.lastname: Clowry
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D064032:Calbindin 2 / Q000235:genetics; D002455:Cell Division; D059330:GABAergic Neurons / Q000166:cytology / Q000378:metabolism*; D015870:Gene Expression; D005968:Glutamate Decarboxylase / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007395:Interneurons / Q000166:cytology / Q000378:metabolism*; D019579:Neocortex / Q000196:embryology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D000076104:Oligodendrocyte Transcription Factor 2; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D064032:Calbindin 2; D005968:Glutamate Decarboxylase; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D014157:Transcription Factors; C065500:ASCL1 protein, human; C576764:CALB2 protein, human; C088334:Distal-less homeobox proteins; C405708:OLIG2 protein, human; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2
keywords: DLX genes; GABA; GABRB3; cerebral cortex; inhibitory interneurons; neurodevelopmental disorders
references.citation: J Neurosci. 2000 Mar 1;20(5):1858-68
references.pmid: 10684887
references.citation: J Comp Neurol. 1995 Aug 14;359(1):144-53
references.pmid: 8557843
references.citation: Clin Genet. 2008 May;73(5):413-23
references.pmid: 18394003
references.citation: Cell. 2011 Jul 8;146(1):18-36
references.pmid: 21729779
references.citation: Nat Rev Neurosci. 2009 Oct;10(10):724-35
references.pmid: 19763105
references.citation: J Comput Biol. 2005 Oct;12(8):1047-64
references.pmid: 16241897
references.citation: Dev Neurobiol. 2011 Jan 1;71(1):92-106
references.pmid: 21154913
references.citation: Mol Psychiatry. 2002;7(3):311-6
references.pmid: 11920158
references.citation: J Comp Neurol. 2005 Oct 17;491(2):109-22
references.pmid: 16127688
references.citation: Genome Biol. 2002 Jun 18;3(7):RESEARCH0034
references.pmid: 12184808
references.citation: Cereb Cortex. 2012 Dec;22(12):2820-30
references.pmid: 22178710
references.citation: Nature. 2011 Oct 26;478(7370):483-9
references.pmid: 22031440
references.citation: Cereb Cortex. 2011 Aug;21(8):1771-82
references.pmid: 21139075
references.citation: Dev Neurobiol. 2008 Dec;68(14):1549-64
references.pmid: 18814314
references.citation: Cereb Cortex. 2009 Sep;19(9):2196-207
references.pmid: 19234067
references.citation: J Neurosci. 2004 Mar 17;24(11):2612-22
references.pmid: 15028753
references.citation: Nat Neurosci. 2002 Apr;5(4):308-15
references.pmid: 11896398
references.citation: Neuron. 2002 Dec 19;36(6):1051-61
references.pmid: 12495621
references.citation: J Comp Neurol. 1998 Aug 10;397(4):493-518
references.pmid: 9699912
references.citation: J Physiol. 2009 May 1;587(Pt 9):1873-9
references.pmid: 19153158
references.citation: Neuroscientist. 2005 Jun;11(3):199-205
references.pmid: 15911869
references.citation: Cereb Cortex. 2008 Jun;18(6):1455-65
references.pmid: 17947347
references.citation: Neuron. 2001 May;30(2):319-33
references.pmid: 11394996
references.citation: Early Hum Dev. 1993 Mar;32(2-3):131-49
references.pmid: 8486116
references.citation: Neuron. 2005 Nov 23;48(4):591-604
references.pmid: 16301176
references.citation: Nat Rev Neurosci. 2012 Jan 18;13(2):107-20
references.pmid: 22251963
references.citation: Cereb Cortex. 2000 Sep;10(9):899-909
references.pmid: 10982750
references.citation: Nat Rev Neurosci. 2010 Feb;11(2):100-13
references.pmid: 20087360
references.citation: J Neurosci. 2010 Apr 14;30(15):5334-45
references.pmid: 20392955
references.citation: J Comp Neurol. 1992 Dec 22;326(4):501-26
references.pmid: 1484122
references.citation: J Comp Neurol. 2005 Jun 13;486(4):344-60
references.pmid: 15846784
references.citation: Mol Cell Neurosci. 1999 Oct-Nov;14(4-5):355-69
references.pmid: 10588390
references.citation: Dev Neurobiol. 2011 Jan 1;71(1):10-7
references.pmid: 21154906
references.citation: Cereb Cortex. 2002 Dec;12(12):1225-36
references.pmid: 12427674
references.citation: J Anat. 2010 Oct;217(4):276-88
references.pmid: 20979582
references.citation: J Anat. 2010 Oct;217(4):368-80
references.pmid: 20727056
references.citation: Trends Neurosci. 2000 Mar;23(3):126-31
references.pmid: 10675917
references.citation: Development. 2002 Nov;129(21):5029-40
references.pmid: 12397111
references.citation: Brain. 1999 Oct;122 ( Pt 10):1807-22
references.pmid: 10506085
references.citation: Dev Neurobiol. 2011 Jan 1;71(1):18-33
references.pmid: 21154907
references.citation: J Neuropathol Exp Neurol. 2007 Jul;66(7):566-75
references.pmid: 17620982
references.citation: Curr Opin Neurobiol. 2002 Feb;12(1):14-25
references.pmid: 11861160
references.citation: Histopathology. 1990 Dec;17(6):489-503
references.pmid: 2076881
references.citation: Nature. 2010 Mar 25;464(7288):554-561
references.pmid: 20154730
references.citation: Cereb Cortex. 2003 Oct;13(10):1072-83
references.pmid: 12967924
references.citation: Development. 1999 Feb;126(3):525-34
references.pmid: 9876181
references.citation: Neuroscientist. 2007 Jun;13(3):268-79
references.pmid: 17519369
references.citation: J Neurosci. 2010 Feb 3;30(5):1582-94
references.pmid: 20130169
references.citation: Neuron. 1991 Jul;7(1):91-100
references.pmid: 2069816
references.citation: Eur J Neurosci. 2008 Oct;28(8):1449-56
references.pmid: 18973570
references.citation: Annu Rev Neurosci. 2003;26:441-83
references.pmid: 12626695
references.citation: Mech Dev. 2000 Dec;99(1-2):143-8
references.pmid: 11091082
references.citation: Neurosignals. 2012;20(3):168-89
references.pmid: 22572780
references.citation: Nature. 2002 Jun 6;417(6889):645-9
references.pmid: 12050665
references.citation: Proc Natl Acad Sci U S A. 2007 Nov 6;104(45):17849-54
references.pmid: 17978184
references.citation: Cereb Cortex. 2008 Jul;18(7):1536-48
references.pmid: 17965125
references.citation: J Comp Neurol. 1997 May 19;381(4):389-410
references.pmid: 9136798
references.citation: Dev Growth Differ. 2009 Apr;51(3):299-323
references.pmid: 19379279
references.citation: Obstet Gynecol. 1984 Jan;63(1):26-32
references.pmid: 6691014
references.citation: Eur J Neurosci. 2007 Mar;25(6):1767-79
references.pmid: 17432964
references.citation: Cereb Cortex. 2011 Jun;21(6):1395-407
references.pmid: 21060114
references.citation: J Autism Dev Disord. 2013 Jan;43(1):68-79
references.pmid: 22555366
references.citation: Anat Embryol (Berl). 1990;182(4):375-400
references.pmid: 2252222
references.citation: J Neurosci. 1996 Oct 1;16(19):6146-56
references.pmid: 8815897
references.citation: J Neurosci. 2007 Jul 18;27(29):7786-98
references.pmid: 17634372
references.citation: Prog Brain Res. 2012;195:45-70
references.pmid: 22230622
references.citation: J Comp Neurol. 1995 Oct 9;361(1):177-92
references.pmid: 8550878
references.citation: J Neurosci. 2000 Aug 1;20(15):5764-74
references.pmid: 10908617
references.citation: Cereb Cortex. 2012 Jun;22(6):1343-59
references.pmid: 21862448
references.citation: J Neurosci. 2007 Apr 18;27(16):4233-42
references.pmid: 17442807
references.citation: J Comp Neurol. 1997 Apr 21;380(4):495-506
references.pmid: 9087528
references.citation: J Comp Neurol. 1999 Sep 20;412(2):241-54
references.pmid: 10441754
references.citation: Cereb Cortex. 2009 Sep;19(9):1953-6
references.pmid: 19429862
references.citation: Cereb Cortex. 2009 Aug;19(8):1795-805
references.pmid: 19015375
references.citation: J Neurosci. 2007 May 9;27(19):5012-22
references.pmid: 17494687
references.citation: J Neurosci. 1994 Mar;14(3 Pt 2):1834-55
references.pmid: 8126575
references.citation: J Neurosci. 2005 Aug 3;25(31):7268-77
references.pmid: 16079409
references.citation: Nat Rev Neurosci. 2005 Apr;6(4):312-24
references.pmid: 15803162
references.citation: J Comp Neurol. 1994 Mar 1;341(1):95-116
references.pmid: 8006226
references.citation: J Anat. 2010 Oct;217(4):300-11
references.pmid: 20579172
references.citation: J Neurosci. 2011 Feb 16;31(7):2413-20
references.pmid: 21325508
references.citation: J Neurosci. 2007 Mar 21;27(12):3078-89
references.pmid: 17376969
references.citation: J Neurosci. 2001 Aug 1;21(15):5607-19
references.pmid: 11466432
references.citation: Pharmacol Rev. 2008 Sep;60(3):243-60
references.pmid: 18790874
references.citation: Adv Anat Embryol Cell Biol. 2002;165:III-IX, 1-92
references.pmid: 12236093
references.citation: Front Neuroanat. 2009 Jun 01;3:5
references.pmid: 19521542
references.citation: J Neurosci. 2008 Dec 10;28(50):13582-91
references.pmid: 19074032
references.citation: Neuron. 1995 Dec;15(6):1287-98
references.pmid: 8845153
references.citation: Cereb Cortex. 2009 Feb;19(2):249-62
references.pmid: 18477686