title: Chemokines induce axon outgrowth downstream of Hepatocyte Growth Factor and TCF/β-catenin signaling.
abstract: Axon morphogenesis is a complex process regulated by a variety of secreted molecules, including morphogens and growth factors, resulting in the establishment of the neuronal circuitry. Our previous work demonstrated that growth factors [Neurotrophins (NT) and Hepatocyte Growth Factor (HGF)] signal through β-catenin during axon morphogenesis. HGF signaling promotes axon outgrowth and branching by inducing β-catenin phosphorylation at Y142 and transcriptional regulation of T-Cell Factor (TCF) target genes. Here, we asked which genes are regulated by HGF signaling during axon morphogenesis. An array screening indicated that HGF signaling elevates the expression of chemokines of the CC and CXC families. In line with this, CCL7, CCL20, and CXCL2 significantly increase axon outgrowth in hippocampal neurons. Experiments using blocking antibodies and chemokine receptor antagonists demonstrate that chemokines act downstream of HGF signaling during axon morphogenesis. In addition, qPCR data demonstrates that CXCL2 and CCL5 expression is stimulated by HGF through Met/b-catenin/TCF pathway. These results identify CC family members and CXCL2 chemokines as novel regulators of axon morphogenesis downstream of HGF signaling.
authors: Depatments of Basic Medical Science and Experimental Medicine, IRBLleida-University of Lleida Lleida, Spain.
authors: Deepshikha
authors: D
authors: Bhardwaj
authors: Mireia
authors: M
authors: Náger
authors: Judith
authors: J
authors: Camats
authors: Monica
authors: M
authors: David
authors: Alberto
authors: A
authors: Benguria
authors: Ana
authors: A
authors: Dopazo
authors: Carles
authors: C
authors: Cantí
authors: Judit
authors: J
authors: Herreros
keywords: axon; beta-catenin; chemokine; hepatocyte growth factor; hippocampal neurons; neurite outgrowth
references: Cell. 1996 Aug 9;86(3):391-9
references: 8756721
references: Oncogene. 2004 Jul 8;23(31):5387-93
references: 15064724
references: Cell. 2012 Jun 8;149(6):1245-56
references: 22682247
references: Nat Neurosci. 2006 Oct;9(10):1284-93
references: 16964252
references: Neuron. 2005 Sep 1;47(5):667-79
references: 16129397
references: Nature. 1998 Jun 11;393(6685):595-9
references: 9634238
references: Neuroscience. 2002;115(1):295-305
references: 12401342
references: Stem Cells Transl Med. 2012 Oct;1(10):732-9
references: 23197665
references: Nature. 1996 Aug 15;382(6592):638-42
references: 8757136
references: Bioinformatics. 2003 Jan 22;19(2):185-93
references: 12538238
references: Mol Cell. 2009 Nov 25;36(4):547-59
references: 19941816
references: Nat Neurosci. 1999 Mar;2(3):213-7
references: 10195212
references: Exp Cell Res. 2006 Nov 1;312(18):3620-30
references: 16952352
references: Oncogene. 2013 Oct 17;32(42):5048-57
references: 23246962
references: J Neurosci. 2011 Nov 9;31(45):16241-50
references: 22072675
references: J Biol Chem. 1998 Apr 24;273(17):10095-8
references: 9553055
references: J Cell Sci. 2008 Aug 15;121(Pt 16):2718-30
references: 18664491
references: J Neurosci. 2003 Jun 15;23(12):5123-30
references: 12832536
references: J Biol Chem. 2000 Nov 24;275(47):36626-31
references: 10969084
references: J Cell Biol. 2006 Jul 17;174(2):289-99
references: 16831887
references: J Neurochem. 2009 May;109(4):1157-67
references: 19302476
references: Eur J Neurosci. 2005 Oct;22(8):1831-9
references: 16262623
references: J Neurosci. 2008 Mar 26;28(13):3277-90
references: 18367595
references: Nat Rev Neurosci. 2005 May;6(5):351-62
references: 15832199
references: J Neurosci. 2008 Nov 12;28(46):11792-5
references: 19005041
references: Development. 2002 Sep;129(18):4249-60
references: 12183377
references: J Neurosci. 2003 Aug 27;23(21):7922-30
references: 12944523
references: Cell. 2004 Oct 1;119(1):97-108
references: 15454084
references: Exp Cell Res. 2008 Jun 10;314(10):2123-30
references: 18420193
references: Eur J Neurosci. 2000 Oct;12(10):3453-61
references: 11029614
references: Stem Cells. 2008 Jul;26(7):1891-900
references: 18436867
references: EMBO J. 2012 Jun 13;31(12):2697-704
references: 22617419
references: Cancer Res. 2013 Feb 1;73(3):1201-10
references: 23243025
references: Neuron. 2003 Nov 13;40(4):719-31
references: 14622577
references: Immunity. 2000 Feb;12(2):121-7
references: 10714678
references: Glia. 2011 Jan;59(1):119-31
references: 20967887
references: Cancer Res. 2002 Apr 1;62(7):2064-71
references: 11929826
references: Cold Spring Harb Perspect Biol. 2010 Feb;2(2):a002915
references: 20182623
references: Curr Drug Targets. 2012 Feb;13(2):166-72
references: 22204316
references: J Neurosci. 2011 Feb 2;31(5):1739-45
references: 21289183
references: Proc Natl Acad Sci U S A. 2002 May 14;99(10):7090-5
references: 11983855
references: J Neurosci. 2008 Feb 13;28(7):1613-24
references: 18272682
references: J Neurosci. 2005 Apr 20;25(16):3995-4003
references: 15843601
references: Mol Cancer Ther. 2008 Mar;7(3):521-9
references: 18347139
references: Nat Neurosci. 2003 Nov;6(11):1169-77
references: 14528308
references: Exp Neurol. 2007 Oct;207(2):195-202
references: 17678646
references: Neuron. 2011 Jan 13;69(1):77-90
references: 21220100
references: Nat Neurosci. 2002 Sep;5(9):843-8
references: 12161754
references: Neuron. 2002 Jul 3;35(1):91-105
references: 12123611
references: Development. 2012 Jul;139(14):2604-13
references: 22696293
references: J Neurosci. 2002 Sep 1;22(17):7586-95
references: 12196582
references: Nat Rev Neurosci. 2003 Jun;4(6):444-55
references: 12778117
references: Neuron. 2011 Jan 13;69(1):61-76
references: 21220099
references: J Neurosci Res. 2010 Nov 1;88(14):3011-23
references: 20722074
references: Science. 2004 Mar 5;303(5663):1483-7
references: 15001769
references: J Biol Chem. 1995 Nov 17;270(46):27780-7
references: 7499247
references: Annu Rev Immunol. 2000;18:217-42
references: 10837058
references: Nat Rev Drug Discov. 2005 Oct;4(10):834-44
references: 16224455
references: Nat Rev Neurosci. 2003 Apr;4(4):299-309
references: 12671646
references: J Cell Sci. 2005 Mar 1;118(Pt 5):1071-80
references: 15731012
references: J Cell Sci. 2012 Nov 1;125(Pt 21):5015-25
references: 22976302
references: J Neurosci. 2008 Aug 13;28(33):8344-53
references: 18701697