Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
May-2016 Volume 13 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
May-2016 Volume 13 Issue 5

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

CXCL12/CXCR4 signaling pathway regulates cochlear development in neonatal mice

  • Authors:
    • Wen Zhang
    • Ji‑Zhou Sun
    • Yu Han
    • Jun Chen
    • Hui Liu
    • Ye Wang
    • Bo Yue
    • Yang Chen
  • View Affiliations / Copyright

    Affiliations: Department of Otolaryngology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China, Department of Otolaryngology, Xi'an XD Group Hospital, Xi'an, Shaanxi 710077, P.R. China, Department of Otolaryngology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China
  • Pages: 4357-4364
    |
    Published online on: April 4, 2016
       https://doi.org/10.3892/mmr.2016.5085
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Chemotactic cytokines (chemokines) are a highly conserved class of secreted signaling molecules that are important in various cellular processes. CXC chemokine ligand 12 (CXCL12) and its receptor, CXC chemokine receptor 4 (CXCR4) have been previously reported to be crucial for the establishment of neural networks in different neuronal systems. However, it is unclear whether the CXCL12/CXCR4 signaling pathway regulates the development of the cochlea. The current study investigated the effects of the CXCL12/CXCR4 signaling pathway on cochlear development in neonatal mice. The expression levels of CXCL12 and CXCR4 were detected using immunofluorescence, reverse transcription‑quantitative polymerase chain reaction and western blot analysis demonstrating that CXCL12 and CXCR4 expression were significantly increased during cochlear development in neonatal mice. Treatment of spiral ganglion neurons with CXCL12 significantly decreased the protein expression levels of caspase‑3 and cleaved caspase‑3, indicating that CXCL12/CXCR4 signaling increased cell survival of spiral ganglion neurons. Furthermore, CXCL12 treatment significantly increased the number and length of neurites extending from spiral ganglion neurons. By contrast, the in vitro effects of CXCL12 were significantly abrogated by AMD100, a CXCR4 antagonist. Additionally, inhibiting CXCL12/CXCR4 signaling in neonatal mice significantly reduced the cell number and altered the morphology of spiral ganglion neurons in vivo. Thus, the present study indicates that the CXCL12/CXCR4 signaling pathway is important during the development of cochleae in neonatal mice.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Bok J, Zenczak C, Hwang CH and Wu DK: Auditory ganglion source of Sonic hedgehog regulates timing of cell cycle exit and differentiation of mammalian cochlear hair cells. Proc Natl Acad Sci USA. 110:13869–13874. 2013. View Article : Google Scholar : PubMed/NCBI

2 

Tateya T, Imayoshi I, Tateya I, Hamaguchi K, Torii H, Ito J and Kageyama R: Hedgehog signaling regulates prosensory cell properties during the basal-to-apical wave of hair cell differentiation in the mammalian cochlea. Development. 140:3848–3857. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Barclay M, Ryan AF and Housley GD: Type I vs type II spiral ganglion neurons exhibit differential survival and neuritogenesis during cochlear development. Neural Dev. 6:332011. View Article : Google Scholar : PubMed/NCBI

4 

Leake PA, Hradek GT, Hetherington AM and Stakhovskaya O: Brain-derived neurotrophic factor promotes cochlear spiral ganglion cell survival and function in deafened, developing cats. J Comp Neurol. 519:1526–1545. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Dabdoub A, Puligilla C, Jones JM, Fritzsch B, Cheah KS, Pevny LH and Kelley MW: Sox2 signaling in prosensory domain specification and subsequent hair cell differentiation in the developing cochlea. Proc Natl Acad Sci USA. 105:18396–18401. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Yang S, Edman LC, Sánchez-Alcañiz JA, Fritz N, Bonilla S, Hecht J, Uhlén P, Pleasure SJ, Villaescusa JC, Marín O and Arenas E: Cxcl12/Cxcr4 signaling controls the migration and process orientation of A9-A10 dopaminergic neurons. Development. 140:4554–4564. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Zou YR, Kottmann AH, Kuroda M, Taniuchi I and Littman DR: Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature. 393:595–599. 1998. View Article : Google Scholar : PubMed/NCBI

8 

Nagasawa T: CXC chemokine ligand 12 (CXCL12) and its receptor CXCR4. J Mol Med Berl. 92:433–439. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Ma Q, Jones D, Borghesani PR, Segal RA, Nagasawa T, Kishimoto T, Bronson RT and Springer TA: Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice. Proc Natl Acad Sci USA. 95:9448–9453. 1998. View Article : Google Scholar : PubMed/NCBI

10 

Zhu Y, Matsumoto T, Mikami S, Nagasawa T and Murakami F: SDF1/CXCR4 signalling regulates two distinct processes of precerebellar neuronal migration and its depletion leads to abnormal pontine nuclei formation. Development. 136:1919–1928. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Stumm RK, Zhou C, Ara T, Lazarini F, Dubois-Dalcq M, Nagasawa T, Höllt V and Schulz S: CXCR4 regulates interneuron migration in the developing neocortex. J Neurosci. 23:5123–5130. 2003.PubMed/NCBI

12 

Lieberam I, Agalliu D, Nagasawa T, Ericson J and Jessell TM: A Cxcl12-CXCR4 chemokine signaling pathway defines the initial trajectory of mammalian motor axons. Neuron. 47:667–679. 2005. View Article : Google Scholar : PubMed/NCBI

13 

García-Hernández S, Potashner SJ and Morest DK: Role of fibroblast growth factor 8 in neurite outgrowth from spiral ganglion neurons in vitro. Brain Res. 1529:39–45. 2013. View Article : Google Scholar : PubMed/NCBI

14 

Livak and Schmittgen: Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCt method. Methods. 25:402–408. 2001. View Article : Google Scholar

15 

Xu N, Engbers J, Khaja S, Xu L, Clark JJ and Hansen MR: Influence of cAMP and protein kinase A on neurite length from spiral ganglion neurons. Hear Res. 283:33–44. 2012. View Article : Google Scholar :

16 

Wang F, Gao X, Chen J, Liu SL, Wang FY, Hei RY, Chen Y and Qiu JH: Effect of early postnatal air-conduction auditory deprivation on the development and function of the rat spiral ganglion. J Laryngol Otol. 125:917–923. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Peng H, Kolb R, Kennedy JE and Zheng J: Differential expression of CXCL12 and CXCR4 during human fetal neural progenitor cell differentiation. J Neuroimmune Pharmacol. 2:251–258. 2007. View Article : Google Scholar : PubMed/NCBI

18 

Schols D, Struyf S, Van Damme J, Esté JA, Henson G and De Clercq E: Inhibition of T-tropic HIV strains by selective antagonization of the chemokine receptor CXCR4. J Exp Med. 186:1383–1388. 1997. View Article : Google Scholar : PubMed/NCBI

19 

Hartnick CJ, Staecker H, Malgrange B, Lefebvre PP, Liu W, Moonen G and Van de Water TR: Neurotrophic effects of BDNF and CNTF, alone and in combination, on postnatal day 5 rat acoustic ganglion neurons. J Neurobiol. 30:246–254. 1996. View Article : Google Scholar : PubMed/NCBI

20 

Mullen LM, Pak KK, Chavez E, Kondo K, Brand Y and Ryan AF: Ras/p38 and PI3K/Akt but not Mek/Erk signaling mediate BDNF-induced neurite formation on neonatal cochlear spiral ganglion explants. Brain Res. 1430:25–34. 2012. View Article : Google Scholar

21 

Aletsee C, Beros A, Mullen L, Palacios S, Pak K, Dazert S and Ryan AF: Ras/MEK but not p38 signaling mediates NT-3-induced neurite extension from spiral ganglion neurons. J Assoc Res Otolaryngol. 2:377–387. 2001. View Article : Google Scholar

22 

Li M and Ransohoff RM: Multiple roles of chemokine CXCL12 in the central nervous system: A migration from immunology to neurobiology. Prog Neurobiol. 84:116–131. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Banisadr G, Fontanges P, Haour F, Kitabgi P, Rostène W and Mélik Parsadaniantz S: Neuroanatomical distribution of CXCR4 in adult rat brain and its localization in cholinergic and dopaminergic neurons. Eur J Neurosci. 16:1661–1671. 2002. View Article : Google Scholar : PubMed/NCBI

24 

Krumbholz M, Theil D, Cepok S, Hemmer B, Kivisäkk P, Ransohoff RM, Hofbauer M, Farina C, Derfuss T, Hartle C, et al: Chemokines in multiple sclerosis: CXCL12 and CXCL13 up-regulation is differentially linked to CNS immune cell recruitment. Brain. 129:200–211. 2006. View Article : Google Scholar

25 

Stumm RK, Rummel J, Junker V, Culmsee C, Pfeiffer M, Krieglstein J, Höllt V and Schulz S: A dual role for the SDF-1/CXCR4 chemokine receptor system in adult brain: Isoform-selective regulation of SDF-1 expression modulates CXCR4-dependent neuronal plasticity and cerebral leukocyte recruitment after focal ischemia. J Neurosci. 22:5865–5878. 2002.PubMed/NCBI

26 

Oh SB, Tran PB, Gillard SE, Hurley RW, Hammond DL and Miller RJ: Chemokines and glycoprotein120 produce pain hypersensitivity by directly exciting primary nociceptive neurons. J Neurosci. 21:5027–5035. 2001.PubMed/NCBI

27 

Limatola C, Giovannelli A, Maggi L, Ragozzino D, Castellani L, Ciotti MT, Vacca F, Mercanti D, Santoni A and Eusebi F: SDF-1α-mediated modulation of synaptic transmission in rat cerebellum. Eur J Neurosci. 12:2497–2504. 2000. View Article : Google Scholar : PubMed/NCBI

28 

Gillard SE, Lu M, Mastracci RM and Miller RJ: Expression of functional chemokine receptors by rat cerebellar neurons. J Neuroimmunol. 124:16–28. 2002. View Article : Google Scholar : PubMed/NCBI

29 

Ragozzino D, Renzi M, Giovannelli A and Eusebi F: Stimulation of chemokine CXC receptor 4 induces synaptic depression of evoked parallel fibers inputs onto Purkinje neurons in mouse cerebellum. J Neuroimmunol. 127:30–36. 2002. View Article : Google Scholar : PubMed/NCBI

30 

Kilpatrick LA, Zhu J, Lee FS and Lang H: Role of stromal cell-derived factor-1 expression in the injured mouse auditory nerve. Otolaryngol Head Neck Surg. 145:1007–1015. 2011. View Article : Google Scholar : PubMed/NCBI

31 

Zhang PZ, He Y, Jiang XW, Chen FQ, Chen Y, Xue T, Zhou K, Li X, Wang Y, Wu YX, et al: Up-regulation of stromal cell-derived factor-1 enhances migration of transplanted neural stem cells to injury region following degeneration of spiral ganglion neurons in the adult rat inner ear. Neurosci Lett. 534:101–106. 2013. View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhang W, Sun JZ, Han Y, Chen J, Liu H, Wang Y, Yue B and Chen Y: CXCL12/CXCR4 signaling pathway regulates cochlear development in neonatal mice. Mol Med Rep 13: 4357-4364, 2016.
APA
Zhang, W., Sun, J., Han, Y., Chen, J., Liu, H., Wang, Y. ... Chen, Y. (2016). CXCL12/CXCR4 signaling pathway regulates cochlear development in neonatal mice. Molecular Medicine Reports, 13, 4357-4364. https://doi.org/10.3892/mmr.2016.5085
MLA
Zhang, W., Sun, J., Han, Y., Chen, J., Liu, H., Wang, Y., Yue, B., Chen, Y."CXCL12/CXCR4 signaling pathway regulates cochlear development in neonatal mice". Molecular Medicine Reports 13.5 (2016): 4357-4364.
Chicago
Zhang, W., Sun, J., Han, Y., Chen, J., Liu, H., Wang, Y., Yue, B., Chen, Y."CXCL12/CXCR4 signaling pathway regulates cochlear development in neonatal mice". Molecular Medicine Reports 13, no. 5 (2016): 4357-4364. https://doi.org/10.3892/mmr.2016.5085
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang W, Sun JZ, Han Y, Chen J, Liu H, Wang Y, Yue B and Chen Y: CXCL12/CXCR4 signaling pathway regulates cochlear development in neonatal mice. Mol Med Rep 13: 4357-4364, 2016.
APA
Zhang, W., Sun, J., Han, Y., Chen, J., Liu, H., Wang, Y. ... Chen, Y. (2016). CXCL12/CXCR4 signaling pathway regulates cochlear development in neonatal mice. Molecular Medicine Reports, 13, 4357-4364. https://doi.org/10.3892/mmr.2016.5085
MLA
Zhang, W., Sun, J., Han, Y., Chen, J., Liu, H., Wang, Y., Yue, B., Chen, Y."CXCL12/CXCR4 signaling pathway regulates cochlear development in neonatal mice". Molecular Medicine Reports 13.5 (2016): 4357-4364.
Chicago
Zhang, W., Sun, J., Han, Y., Chen, J., Liu, H., Wang, Y., Yue, B., Chen, Y."CXCL12/CXCR4 signaling pathway regulates cochlear development in neonatal mice". Molecular Medicine Reports 13, no. 5 (2016): 4357-4364. https://doi.org/10.3892/mmr.2016.5085
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team