Prox1 is required for granule cell maturation and intermediate progenitor maintenance during brain neurogenesis.
The dentate gyrus has an important role in learning and memory, and adult neurogenesis in the subgranular zone of the dentate gyrus may play a role in the acquisition of new memories. The homeobox gene Prox1 is expressed in the dentate gyrus during embryonic development and adult neurogenesis. Here we show that Prox1 is necessary for the maturation of granule cells in the dentate gyrus during development and for the maintenance of intermediate progenitors during adult neurogenesis. We also demonstrate that Prox1-expressing intermediate progenitors are required for adult neural stem cell self-maintenance in the subgranular zone; thus, we have identified a previously unknown non-cell autonomous regulatory feedback mechanism that controls adult neurogenesis in this region of the mammalian brain. Finally, we show that the ectopic expression of Prox1 induces premature differentiation of neural stem cells.
Lavado
Alfonso
A
Department of Genetics & Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, United States of America.
Lagutin
Oleg V
OV
Chow
Lionel M L
LM
Baker
Suzanne J
SJ
Oliver
Guillermo
G
D053687:Adult Stem Cells / Q000166:cytology; D000818:Animals; D001921:Brain / Q000196:embryology; D002454:Cell Differentiation; D018891:Dentate Gyrus / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology*; D055495:Neurogenesis / Q000187:drug effects*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D000098551:Prospero-Related Homeobox 1 Protein
D018398:Homeodomain Proteins; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein
Nat Rev Neurosci. 2010 May;11(5):339-50
20354534
J Neurosci. 2000 Aug 15;20(16):6095-105
10934259
Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20558-63
18077357
Nat Genet. 2005 Oct;37(10):1072-81
16170315
Neuroscience. 2007 May 11;146(2):604-16
17368742
J Neurosci. 1996 Mar 15;16(6):2027-33
8604047
Dev Neurosci. 2005 Mar-Aug;27(2-4):93-9
16046842
Learn Mem. 2009 Jan 29;16(2):147-54
19181621
Nature. 2003 Oct 23;425(6960):841-6
14574413
Development. 1992 Sep;116(1):201-11
1483388
Exp Neurol. 2005 Dec;196(2):342-51
16168988
Nat Immunol. 2005 Mar;6(3):314-22
15665828
J Neurosci. 2004 Jan 7;24(1):121-6
14715945
J Neurosci. 2008 Apr 2;28(14):3707-17
18385329
Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):865-70
10639171
Mol Cell Neurosci. 2003 Nov;24(3):603-13
14664811
Nat Genet. 1999 Mar;21(3):318-22
10080188
Nat Rev Genet. 2008 Feb;9(2):115-28
18202695
J Comp Neurol. 1965 Jun;124(3):319-35
5861717
Development. 2000 Feb;127(3):457-67
10631167
Genes Dev. 1999 Jul 1;13(13):1647-52
10398678
J Comp Neurol. 2003 Dec 1;467(1):1-10
14574675
Science. 1992 Mar 27;255(5052):1707-10
1553558
J Clin Invest. 2007 Apr;117(4):961-70
17404619
Mech Dev. 1993 Nov;44(1):3-16
7908825
Nat Genet. 2003 May;34(1):53-8
12692551
Curr Biol. 1996 Oct 1;6(10):1307-16
8939573
J Neurosci. 2000 May 15;20(10):3714-24
10804213
Nature. 1967 Jun 10;214(5093):1098-101
6053066
Cell Stem Cell. 2007 Nov;1(5):515-28
18371391
Trends Neurosci. 2004 Aug;27(8):447-52
15271491
Development. 2008 Feb;135(3):441-50
18094027
Development. 2008 May;135(9):1575-87
18356248
Toxicol Sci. 2004 Nov;82(1):341-58
15319485
PLoS One. 2007 Nov 28;2(11):e1221
18043734
Proc Natl Acad Sci U S A. 2009 Apr 21;106(16):6685-90
19346468
Nat Med. 1998 Nov;4(11):1313-7
9809557
Development. 2008 Jun;135(11):2031-41
18448566
J Neurosci. 2001 Sep 15;21(18):7153-60
11549726
Development. 2000 Feb;127(3):469-82
10631168
J Neurosci. 2009 Oct 28;29(43):13532-42
19864566
Nat Neurosci. 2009 Sep;12(9):1090-2
19701197
Dev Cell. 2009 Feb;16(2):196-208
19217422
Neuron. 2008 May 22;58(4):519-31
18498734
Neuron. 2004 Mar 4;41(5):683-6
15003168
Dev Dyn. 2007 Feb;236(2):518-24
17117441
Neuron. 2008 Oct 9;60(1):56-69
18940588
Nature. 2005 Jun 16;435(7044):959-63
15959515
Neuroscience. 2008 Jun 23;154(2):521-9
18502050
Nat Neurosci. 2008 Aug;11(8):888-93
18587391
Stem Cells. 2006 Nov;24(11):2437-47
16888285
Nat Neurosci. 2009 Sep;12(9):1097-105
19701198
Histochemistry. 1993 Dec;100(6):431-40
7512949
Science. 2007 Feb 16;315(5814):961-6
17303747
J Neurobiol. 1999 Dec;41(4):524-39
10590176
Science. 2008 Mar 21;319(5870):1640-2
18356518
Cell Stem Cell. 2009 Nov 6;5(5):515-26
19896442