The T-box transcription factor Eomes/Tbr2 regulates neurogenesis in the cortical subventricular zone.
The embryonic subventricular zone (SVZ) is a critical site for generating cortical projection neurons; however, molecular mechanisms regulating neurogenesis specifically in the SVZ are largely unknown. The transcription factor Eomes/Tbr2 is transiently expressed in cortical SVZ progenitor cells. Here we demonstrate that conditional inactivation of Tbr2 during early brain development causes microcephaly and severe behavioral deficits. In Tbr2 mutants the number of SVZ progenitor cells is reduced and the differentiation of upper cortical layer neurons is disturbed. Neurogenesis in the adult dentate gyrus but not the subependymal zone is abolished. These studies establish Tbr2 as a key regulator of neurogenesis in the SVZ.
Arnold
Sebastian J
SJ
Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
Huang
Guo-Jen
GJ
Cheung
Amanda F P
AF
Era
Takumi
T
Nishikawa
Shin-Ichi
S
Bikoff
Elizabeth K
EK
Molnár
Zoltán
Z
Robertson
Elizabeth J
EJ
Groszer
Matthias
M
D000818:Animals; D002552:Cerebral Ventricles / Q000166:cytology* / Q000196:embryology; D051379:Mice; D009474:Neurons / Q000166:cytology*; D020825:T-Box Domain Proteins / Q000502:physiology*
C491198:Eomes protein, mouse; D020825:T-Box Domain Proteins
Nature. 2004 Jan 1;427(6969):78-83
14702088
Nature. 1997 Dec 4;390(6659):515-7
9394001
Nat Rev Neurosci. 2006 Nov;7(11):883-90
17033683
Cell. 2007 Jan 12;128(1):29-43
17218253
Cereb Cortex. 2004 Dec;14(12):1408-20
15238450
J Neurosci. 1995 Sep;15(9):6058-68
7666189
Development. 2001 Jun;128(11):1983-93
11493521
Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):3196-201
14963232
Mech Dev. 1999 Jun;84(1-2):133-8
10473127
Science. 2002 Jul 19;297(5580):365-9
12130776
J Comp Neurol. 1982 Aug 1;209(2):113-22
7130449
Nat Genet. 2007 Apr;39(4):454-6
17353897
J Neurosci. 2008 Apr 2;28(14):3707-17
18385329
Nature. 2000 Mar 2;404(6773):95-9
10716450
Nat Rev Neurosci. 2007 Jun;8(6):427-37
17514196
J Neurocytol. 1992 Mar;21(3):185-97
1373183
Cereb Cortex. 2008 Aug;18(8):1865-75
18065723
Cell. 2007 Jun 29;129(7):1377-88
17604725
Neuron. 2008 Feb 7;57(3):378-92
18255031
J Neurosci. 2005 Jul 13;25(28):6533-8
16014714
Cereb Cortex. 2003 Sep;13(9):921-31
12902391
Trends Neurosci. 2004 Aug;27(8):447-52
15271491
Genes Dev. 2002 Jul 15;16(14):1760-5
12130536
Neuron. 2001 Feb;29(2):353-66
11239428
Science. 1974 Feb 1;183(4123):425-7
4203022
J Neurosci. 2005 Jan 5;25(1):247-51
15634788
Nat Neurosci. 2004 Feb;7(2):136-44
14703572
Proc Natl Acad Sci U S A. 2005 Nov 22;102(47):17172-7
16284248
Arch Histol Cytol. 2001 May;64(2):149-58
11436985
Science. 2008 May 16;320(5878):946-9
18487195
Neuron. 1998 Dec;21(6):1273-82
9883721
Development. 2008 Feb;135(3):501-11
18171685
J Comp Neurol. 1990 Nov 15;301(3):365-81
2262596
Cereb Cortex. 2002 Jan;12(1):37-53
11734531
Cereb Cortex. 2008 Aug;18(8):1758-70
18033766
J Anat. 2007 Aug;211(2):164-76
17634059
Dev Biol. 2007 Feb 1;302(1):50-65
16979618