Chemokines Induce Axon Outgrowth Downstream of Hepatocyte Growth Factor and TCF/β-catenin Signaling

Overview

Journal Front Cell Neurosci

Specialty Cell Biology

Date 2013 May 4

PMID 23641195

Citations 19

Authors

Deepshikha Bhardwaj

Mireia Nager

Judith Camats

Monica David

Alberto Benguria

Ana Dopazo

Carles Canti

Judit Herreros

Affiliations

Soon will be listed here.

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.

Citing Articles

Neuronal chemokines: new insights into neuronal communication after injury.

Mesquida-Veny F, Hervera A Neural Regen Res. 2023; 18(11):2379-2380.

PMID: 37282457 PMC: 10360099. DOI: 10.4103/1673-5374.371352.

CXCR4 and CXCL12 signaling regulates the development of extrinsic innervation to the colorectum.

Halasy V, Szocs E, Soos A, Kovacs T, Pecsenye-Fejszak N, Hotta R Development. 2023; 150(8).

PMID: 37039233 PMC: 10263150. DOI: 10.1242/dev.201289.

Nociception-Dependent CCL21 Induces Dorsal Root Ganglia Axonal Growth CCR7-ERK Activation.

Mesquida-Veny F, Martinez-Torres S, Del Rio J, Hervera A Front Immunol. 2022; 13:880647.

PMID: 35911704 PMC: 9331658. DOI: 10.3389/fimmu.2022.880647.

The Importance of CXCL1 in Physiology and Noncancerous Diseases of Bone, Bone Marrow, Muscle and the Nervous System.

Korbecki J, Gassowska-Dobrowolska M, Wojcik J, Szatkowska I, Barczak K, Chlubek M Int J Mol Sci. 2022; 23(8).

PMID: 35457023 PMC: 9024980. DOI: 10.3390/ijms23084205.

An update on Wnt signaling pathway in cancer.

Zhang Y, Zu D, Chen Z, Ying G Transl Cancer Res. 2022; 9(2):1246-1252.

PMID: 35117469 PMC: 8797977. DOI: 10.21037/tcr.2019.12.50.

References

Molenaar M, van de Wetering M, Oosterwegel M, Peterson-Maduro J, Godsave S, Korinek V . XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos. Cell. 1996; 86(3):391-9. DOI: 10.1016/s0092-8674(00)80112-9. View

Berthou S, Aebersold D, Schmidt L, Stroka D, Heigl C, Streit B . The Met kinase inhibitor SU11274 exhibits a selective inhibition pattern toward different receptor mutated variants. Oncogene. 2004; 23(31):5387-93. DOI: 10.1038/sj.onc.1207691. View

Li V, Ng S, Boersema P, Low T, Karthaus W, Gerlach J . Wnt signaling through inhibition of β-catenin degradation in an intact Axin1 complex. Cell. 2012; 149(6):1245-56. DOI: 10.1016/j.cell.2012.05.002. View

Borrell V, Marin O . Meninges control tangential migration of hem-derived Cajal-Retzius cells via CXCL12/CXCR4 signaling. Nat Neurosci. 2006; 9(10):1284-93. DOI: 10.1038/nn1764. View

Lieberam I, Agalliu D, Nagasawa T, Ericson J, Jessell T . A Cxcl12-CXCR4 chemokine signaling pathway defines the initial trajectory of mammalian motor axons. Neuron. 2005; 47(5):667-79. DOI: 10.1016/j.neuron.2005.08.011. View

Zou Y, Kottmann A, Kuroda M, Taniuchi I, Littman D . Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature. 1998; 393(6685):595-9. DOI: 10.1038/31269. View

Reiss K, Mentlein R, Sievers J, Hartmann D . Stromal cell-derived factor 1 is secreted by meningeal cells and acts as chemotactic factor on neuronal stem cells of the cerebellar external granular layer. Neuroscience. 2002; 115(1):295-305. DOI: 10.1016/s0306-4522(02)00307-x. View

Jaerve A, Schira J, Muller H . Concise review: the potential of stromal cell-derived factor 1 and its receptors to promote stem cell functions in spinal cord repair. Stem Cells Transl Med. 2012; 1(10):732-9. PMC: 3659654. DOI: 10.5966/sctm.2012-0068. View

Behrens J, von Kries J, Kuhl M, Bruhn L, Wedlich D, Grosschedl R . Functional interaction of beta-catenin with the transcription factor LEF-1. Nature. 1996; 382(6592):638-42. DOI: 10.1038/382638a0. View

10.

Bolstad B, Irizarry R, Astrand M, Speed T . A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics. 2003; 19(2):185-93. DOI: 10.1093/bioinformatics/19.2.185. View

11.

Ji H, Wang J, Nika H, Hawke D, Keezer S, Ge Q . EGF-induced ERK activation promotes CK2-mediated disassociation of alpha-Catenin from beta-Catenin and transactivation of beta-Catenin. Mol Cell. 2009; 36(4):547-59. PMC: 2784926. DOI: 10.1016/j.molcel.2009.09.034. View

12.

Maina F, Klein R . Hepatocyte growth factor, a versatile signal for developing neurons. Nat Neurosci. 1999; 2(3):213-7. DOI: 10.1038/6310. View

13.

Zeng G, Apte U, Micsenyi A, Bell A, Monga S . Tyrosine residues 654 and 670 in beta-catenin are crucial in regulation of Met-beta-catenin interactions. Exp Cell Res. 2006; 312(18):3620-30. PMC: 1820835. DOI: 10.1016/j.yexcr.2006.08.003. View

14.

Xi Y, Wei Y, Sennino B, Ulsamer A, Kwan I, Brumwell A . Identification of pY654-β-catenin as a critical co-factor in hypoxia-inducible factor-1α signaling and tumor responses to hypoxia. Oncogene. 2012; 32(42):5048-57. PMC: 3871884. DOI: 10.1038/onc.2012.530. View

15.

Rogers J, Morganti J, Bachstetter A, Hudson C, Peters M, Grimmig B . CX3CR1 deficiency leads to impairment of hippocampal cognitive function and synaptic plasticity. J Neurosci. 2011; 31(45):16241-50. PMC: 3236509. DOI: 10.1523/JNEUROSCI.3667-11.2011. View

16.

White J, Lee J, Young P, Hertzberg R, Jurewicz A, Chaikin M . Identification of a potent, selective non-peptide CXCR2 antagonist that inhibits interleukin-8-induced neutrophil migration. J Biol Chem. 1998; 273(17):10095-8. DOI: 10.1074/jbc.273.17.10095. View

17.

David M, Yeramian A, Dunach M, Llovera M, Canti C, Garcia de Herreros A . Signalling by neurotrophins and hepatocyte growth factor regulates axon morphogenesis by differential beta-catenin phosphorylation. J Cell Sci. 2008; 121(Pt 16):2718-30. DOI: 10.1242/jcs.029660. View

18.

Stumm R, Zhou C, Ara T, Lazarini F, Dubois-Dalcq M, Nagasawa T . CXCR4 regulates interneuron migration in the developing neocortex. J Neurosci. 2003; 23(12):5123-30. PMC: 6741192. View

19.

White J, Lee J, Dede K, Imburgia C, Jurewicz A, Chan G . Identification of potent, selective non-peptide CC chemokine receptor-3 antagonist that inhibits eotaxin-, eotaxin-2-, and monocyte chemotactic protein-4-induced eosinophil migration. J Biol Chem. 2000; 275(47):36626-31. DOI: 10.1074/jbc.M006613200. View

20.

Bamji S, Rico B, Kimes N, Reichardt L . BDNF mobilizes synaptic vesicles and enhances synapse formation by disrupting cadherin-beta-catenin interactions. J Cell Biol. 2006; 174(2):289-99. PMC: 2064188. DOI: 10.1083/jcb.200601087. View