title: Targeted deletion of the ERK5 MAP kinase impairs neuronal differentiation, migration, and survival during adult neurogenesis in the olfactory bulb.
abstract: Recent studies have led to the exciting idea that adult-born neurons in the olfactory bulb (OB) may be critical for complex forms of olfactory behavior in mice. However, signaling mechanisms regulating adult OB neurogenesis are not well defined. We recently reported that extracellular signal-regulated kinase (ERK) 5, a MAP kinase, is specifically expressed in neurogenic regions within the adult brain. This pattern of expression suggests a role for ERK5 in the regulation of adult OB neurogenesis. Indeed, we previously reported that conditional deletion of erk5 in adult neurogenic regions impairs several forms of olfactory behavior in mice. Thus, it is important to understand how ERK5 regulates adult neurogenesis in the OB. Here we present evidence that shRNA suppression of ERK5 in adult neural stem/progenitor cells isolated from the subventricular zone (SVZ) reduces neurogenesis in culture. By contrast, ectopic activation of endogenous ERK5 signaling via expression of constitutive active MEK5, an upstream activating kinase for ERK5, stimulates neurogenesis. Furthermore, inducible and conditional deletion of erk5 specifically in the neurogenic regions of the adult mouse brain interferes with cell cycle exit of neuroblasts, impairs chain migration along the rostral migratory stream and radial migration into the OB. It also inhibits neuronal differentiation and survival. These data suggest that ERK5 regulates multiple aspects of adult OB neurogenesis and provide new insights concerning signaling mechanisms governing adult neurogenesis in the SVZ-OB axis.
authors: Toxicology Program in the Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington, United States of America.
authors: Tan
authors: T
authors: Li
authors: Yung-Wei
authors: YW
authors: Pan
authors: Wenbin
authors: W
authors: Wang
authors: Glen
authors: G
authors: Abel
authors: Junhui
authors: J
authors: Zou
authors: Lihong
authors: L
authors: Xu
authors: Daniel R
authors: DR
authors: Storm
authors: Zhengui
authors: Z
authors: Xia
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002465:Cell Movement; D002470:Cell Survival; D002478:Cells, Cultured; D002552:Cerebral Ventricles / Q000166:cytology / Q000201:enzymology; D055786:Gene Knockout Techniques; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D048054:Mitogen-Activated Protein Kinase 7 / Q000172:deficiency / Q000235:genetics*; D058953:Neural Stem Cells / Q000502:physiology; D055495:Neurogenesis; D009474:Neurons / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology*; D061251:Primary Cell Culture
chemical_list: D048054:Mitogen-Activated Protein Kinase 7
references: Learn Mem. 2009 Jan 29;16(2):147-54
references: 19181621
references: J Neurosci. 2012 Mar 21;32(12):4118-32
references: 22442076
references: Ann N Y Acad Sci. 2009 Jul;1170:664-73
references: 19686209
references: Development. 2004 Jan;131(1):217-28
references: 14660435
references: J Neurosci. 2010 Mar 17;30(11):3995-4003
references: 20237270
references: Front Biosci. 2007 Jan 01;12:591-607
references: 17127320
references: Nat Neurosci. 2004 Dec;7(12):1319-28
references: 15543145
references: Nat Rev Neurosci. 2006 Mar;7(3):179-93
references: 16495940
references: PLoS One. 2009 Oct 20;4(10):e7506
references: 19841742
references: Rev Neurosci. 2009;20(5-6):331-46
references: 20397619
references: Prog Neurobiol. 2009 Oct;89(2):162-75
references: 19615423
references: Nature. 2005 Oct 6;437(7060):894-7
references: 16208373
references: Eur J Neurosci. 2002 Nov;16(9):1681-9
references: 12431220
references: Genes Dev. 2012 May 15;26(10):1010-21
references: 22588716
references: Mol Cell Neurosci. 2012 Feb;49(2):97-103
references: 22061967
references: Stem Cells. 2008 May;26(5):1221-30
references: 18323412
references: Curr Opin Neurobiol. 2005 Feb;15(1):121-8
references: 15721754
references: Nat Neurosci. 2001 Oct;4(10):981-8
references: 11544482
references: Prog Neurobiol. 2005 Apr;75(5):321-41
references: 15913880
references: Neuron. 2011 Sep 8;71(5):883-97
references: 21903081
references: Neuron. 2010 Nov 18;68(4):682-94
references: 21092858
references: Neuron. 2003 Sep 11;39(6):937-50
references: 12971894
references: J Biol Chem. 2012 Jul 6;287(28):23306-17
references: 22645146
references: J Neurosci. 2012 May 16;32(20):6947-56
references: 22593063
references: Development. 2005 Jan;132(2):335-44
references: 15604099
references: Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):13211-6
references: 12235363
references: PLoS One. 2009 Sep 15;4(9):e7017
references: 19753118
references: J Neurosci. 2005 Jul 27;25(30):6997-7003
references: 16049175
references: Sci STKE. 2006 Jan 24;2006(319):pe5
references: 16434726
references: J Cell Biol. 2007 Apr 23;177(2):253-64
references: 17452529
references: J Neurosci. 2009 Dec 2;29(48):15245-57
references: 19955377
references: Development. 2009 Jun;136(12):2027-38
references: 19439492
references: Cell Stem Cell. 2011 Jan 7;8(1):59-71
references: 21211782
references: Mol Cell Neurosci. 2011 Jan;46(1):79-88
references: 20801218
references: J Neurosci. 2012 Dec 5;32(49):17788-99
references: 23223298
references: Cell. 2006 Dec 15;127(6):1253-64
references: 17174898
references: Cell Death Differ. 2009 May;16(5):674-83
references: 19148185
references: Mol Brain. 2009 Jun 08;2:16
references: 19505325
references: Stem Cells. 2007 Nov;25(11):2827-36
references: 17673525
references: Proc Natl Acad Sci U S A. 2006 Jun 20;103(25):9697-702
references: 16766652
references: J Neurosci. 2012 Jun 27;32(26):8879-89
references: 22745489
references: Mol Pharmacol. 2010 Jan;77(1):10-6
references: 19858097
references: J Neurosci. 2012 Nov 21;32(47):16892-905
references: 23175841
references: J Neurosci. 2010 Mar 3;30(9):3489-98
references: 20203209
references: Neuron. 2011 May 26;70(4):687-702
references: 21609825
references: J Neurosci. 2005 Jun 1;25(22):5404-12
references: 15930390
references: J Neurosci. 2003 Aug 13;23(19):7326-36
references: 12917366
references: J Neurosci. 2012 May 9;32(19):6444-55
references: 22573667
references: Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8532-7
references: 12826611
references: Annu Rev Neurosci. 2005;28:223-50
references: 16022595
references: Nature. 1998 Oct 15;395(6703):713-6
references: 9790194
references: Traffic. 2007 Aug;8(8):959-69
references: 17547700
references: J Biol Chem. 2013 Jan 25;288(4):2623-31
references: 23223235
references: Nat Neurosci. 2009 Oct;12(10):1248-56
references: 19734891
references: Genes Dev. 2008 Sep 15;22(18):2473-8
references: 18794344
references: Mol Cell Biol. 1999 Jun;19(6):4289-301
references: 10330170
references: J Comp Neurol. 1969 Dec;137(4):433-57
references: 5361244
references: J Biol Chem. 1995 Dec 1;270(48):28897-902
references: 7499418
references: J Neurosci. 2011 May 18;31(20):7551-62
references: 21593340
references: Nat Neurosci. 2009 Dec;12(12):1524-33
references: 19881504
references: BMC Dev Biol. 2001;1:4
references: 11299042
references: Science. 2000 Feb 25;287(5457):1433-8
references: 10688783
references: Development. 2004 Aug;131(15):3805-19
references: 15240551
references: PLoS One. 2009;4(4):e5204
references: 19365559
references: Mol Cell Biol. 2005 Jan;25(1):336-45
references: 15601854
references: Nat Neurosci. 2005 Jul;8(7):865-72
references: 15951811
references: FASEB J. 2010 Jul;24(7):2355-63
references: 20215526
references: Nature. 2005 Oct 27;437(7063):1370-5
references: 16251967
references: Stem Cells. 2010 Nov;28(11):2053-2064
references: 21089118
references: Cell. 1999 Jun 11;97(6):703-16
references: 10380923
references: PLoS One. 2012;7(6):e38664
references: 22761695
references: Glia. 2007 Jan 15;55(2):165-77
references: 17078026
references: J Neurosci. 2009 Jun 24;29(25):7966-77
references: 19553437
references: J Neurosci. 2008 Jun 18;28(25):6439-52
references: 18562615
references: PLoS One. 2012;7(11):e49622
references: 23185386
references: Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1930-5
references: 16446434
references: Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1823-8
references: 10677540
references: J Neurosci. 2002 Jul 15;22(14):6106-13
references: 12122071
references: Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9697-702
references: 15976032
references: J Neurosci. 2008 Mar 5;28(10):2383-93
references: 18322085
references: J Neurosci. 2005 Nov 2;25(44):10105-18
references: 16267218
references: J Biol Chem. 1995 May 26;270(21):12665-9
references: 7759517