title: Asymmetric N-cadherin expression results in synapse dysfunction, synapse elimination, and axon retraction in cultured mouse neurons.
abstract: Synapse elimination and pruning of axon collaterals are crucial developmental events in the refinement of neuronal circuits. While a control of synapse formation by adhesion molecules is well established, the involvement of adhesion molecules in developmental synapse loss is poorly characterized. To investigate the consequences of mis-match expression of a homophilic synaptic adhesion molecule, we analysed an asymmetric, exclusively postsynaptic expression of N-cadherin. This was induced by transfecting individual neurons in cultures of N-cadherin knockout mouse neurons with a N-cadherin expression vector. 2 days after transfection, patch-clamp analysis of AMPA receptor-mediated miniature postsynaptic currents revealed an impaired synaptic function without a reduction in the number of presynaptic vesicle clusters. Long-term asymmetric expression of N-cadherin for 8 days subsequently led to synapse elimination as indicated by a loss of colocalization of presynaptic vesicles and postsynaptic PSD95 protein. We further studied long-term asymmetric N-cadherin expression by conditional, Cre-induced knockout of N-cadherin in individual neurons in cultures of N-cadherin expressing cortical mouse neurons. This resulted in a strong retraction of axonal processes in individual neurons that lacked N-cadherin protein. Moreover, an in vivo asymmetric expression of N-cadherin in the developmentally transient cortico-tectal projection was indicated by in-situ hybridization with layer V neurons lacking N-cadherin expression. Thus, mis-match expression of N-cadherin might contribute to selective synaptic connectivity.
authors: Institute of Neuro- and Sensory Physiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.
authors: Kim N
authors: KN
authors: Pielarski
authors: Bernd
authors: B
authors: van Stegen
authors: Aksana
authors: A
authors: Andreyeva
authors: Katja
authors: K
authors: Nieweg
authors: Kay
authors: K
authors: Jüngling
authors: Christoph
authors: C
authors: Redies
authors: Kurt
authors: K
authors: Gottmann
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D018091:Receptors, AMPA / Q000378:metabolism; D013569:Synapses / Q000187:drug effects* / Q000473:pathology; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism
chemical_list: D015820:Cadherins; D015815:Cell Adhesion Molecules; D018091:Receptors, AMPA
references: FASEB J. 2003 Nov;17(14):2100-2
references: 14500547
references: J Biol Chem. 2001 Nov 23;276(47):43879-86
references: 11571292
references: Dev Biol. 1995 Dec;172(2):466-78
references: 8612964
references: J Neurosci Res. 2008 Feb 1;86(2):223-32
references: 17787017
references: Cell Mol Life Sci. 2008 Nov;65(23):3809-21
references: 18791849
references: Curr Opin Neurobiol. 2011 Feb;21(1):132-43
references: 20832286
references: Proc Natl Acad Sci U S A. 2010 Jun 15;107(24):11116-21
references: 20534458
references: Nat Cell Biol. 2007 Aug;9(8):883-92
references: 17618275
references: J Neurosci. 2006 Jun 28;26(26):6968-78
references: 16807326
references: Neuron. 2007 Nov 8;56(3):456-71
references: 17988630
references: Neuron. 2010 Oct 6;68(1):9-18
references: 20920787
references: Annu Rev Neurosci. 2010;33:473-507
references: 20367446
references: Neuron. 2005 Sep 1;47(5):725-37
references: 16129401
references: Science. 1997 Jan 17;275(5298):356-61
references: 8994026
references: Neuron. 1993 Jun;10(6):991-1006
references: 8318235
references: Nat Neurosci. 2004 Sep;7(9):1003-9
references: 15332090
references: Circ Res. 2005 Feb 18;96(3):346-54
references: 15662031
references: Neuron. 2011 Aug 25;71(4):632-9
references: 21867880
references: Nat Rev Neurosci. 2007 Jan;8(1):11-20
references: 17133224
references: Mol Cell Neurosci. 2004 Dec;27(4):509-21
references: 15555928
references: Neuron. 2007 May 3;54(3):461-77
references: 17481398
references: Curr Opin Cell Biol. 2008 Oct;20(5):567-75
references: 18602471
references: Nat Rev Neurosci. 2001 Dec;2(12):899-909
references: 11733797
references: Nat Cell Biol. 2002 Oct;4(10):798-805
references: 12360290
references: Neuron. 2006 Jul 6;51(1):43-56
references: 16815331
references: Neuroscience. 2001;106(3):505-33
references: 11591453
references: Annu Rev Neurosci. 1999;22:389-442
references: 10202544
references: J Comp Neurol. 1999 May 17;407(4):453-71
references: 10235639
references: J Neurochem. 2006 Jun;97(5):1215-31
references: 16638017
references: Biochem Soc Trans. 2008 Apr;36(Pt 2):149-55
references: 18363555
references: Nature. 2003 Jul 24;424(6947):430-4
references: 12879071
references: Neuron. 2005 May 5;46(3):395-400
references: 15882638
references: Nucleic Acids Res. 1997 Aug 15;25(16):3326-31
references: 9241248
references: Neurosci Lett. 2011 Sep 1;501(3):167-72
references: 21782891
references: Neuron. 2003 Nov 13;40(4):719-31
references: 14622577
references: Int J Dev Biol. 1999 Nov;43(8):831-4
references: 10707907
references: Cell Tissue Res. 2006 Nov;326(2):617-42
references: 16855838
references: J Comp Neurol. 1998 May 4;394(2):205-17
references: 9552126
references: J Cell Biol. 1996 Sep;134(6):1519-29
references: 8830779
references: Curr Opin Neurobiol. 2011 Apr;21(2):208-14
references: 21255999
references: Annu Rev Biochem. 2007;76:267-94
references: 17506641
references: J Neurosci. 2010 Jul 28;30(30):9984-9
references: 20668183
references: Nat Neurosci. 2003 Nov;6(11):1169-77
references: 14528308
references: J Cell Sci Suppl. 1991;15:13-21
references: 1824104
references: Front Biosci. 2003 Jan 01;8:d306-55
references: 12456358
references: Curr Opin Cell Biol. 2007 Oct;19(5):551-6
references: 17936606
references: Development. 1990 Dec;110(4):1341-8
references: 2129226
references: J Neurosci. 2008 Jun 4;28(23):5879-90
references: 18524892
references: Brain Res. 2007 Apr 6;1140:205-15
references: 17173877
references: J Comp Neurol. 2002 Nov 25;453(4):372-88
references: 12389209
references: Brain. 2012 Jul;135(Pt 7):2140-54
references: 22637581
references: Prog Neurobiol. 2000 Aug;61(6):611-48
references: 10775799
references: Proc Natl Acad Sci U S A. 2010 May 25;107(21):9873-8
references: 20457910
references: Neuron. 2002 Jul 3;35(1):91-105
references: 12123611
references: Neuroscience. 2003;117(1):7-18
references: 12605887
references: Neuron. 2001 Nov 20;32(4):673-82
references: 11719207
references: Dev Biol. 2007 Apr 1;304(1):22-33
references: 17222817
references: J Comp Neurol. 2006 Mar 20;495(3):324-35
references: 16440298
references: Nature. 2008 Oct 16;455(7215):903-11
references: 18923512
references: Dev Biol. 1997 Jan 1;181(1):64-78
references: 9015265
references: Neuron. 1988 Mar;1(1):33-43
references: 2856086
references: Neuron. 2000 Apr;26(1):207-17
references: 10798405
references: Neuron. 2002 Jul 3;35(1):77-89
references: 12123610
references: J Cell Biol. 1996 Nov;135(3):767-79
references: 8909549
references: J Cell Biol. 2010 May 3;189(3):589-600
references: 20440002
references: Neuron. 1996 Sep;17(3):423-34
references: 8816706
references: Neuron. 2011 Aug 25;71(4):640-55
references: 21867881
references: Dev Dyn. 1993 May;197(1):26-39
references: 8400409
references: Neuroscientist. 2009 Feb;15(1):90-104
references: 19218233
references: Front Neurosci. 2008 Dec 15;2(2):168-75
references: 19225589
references: J Neurosci. 1998 Sep 1;18(17):6892-904
references: 9712659