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A population of nonneuronal GFRα3-expressing cells in the bone marrow resembles nonmyelinating Schwann cells

  • Jenny Thai
  • Alanna C. Green
  • Lincon A. Stamp
  • Nick J. Spencer
  • Louise E. Purton
  • Jason IvanusicEmail author
Regular Article

Abstract

Artemin is a neurotrophic factor that plays a crucial role in the regulation of neural development and regeneration and has also been implicated in the pathogenesis of inflammatory pain. The receptor for artemin, GFRα3, is expressed by sympathetic and nociceptive sensory neurons, including some that innervate the bone marrow, but it is unclear if it is also expressed in other cell types in the bone marrow. Our goal in the present study was to characterise the expression of GFRα3 in nonneuronal cells in the bone marrow. Immunohistochemical studies revealed that GFRα3-expressing cells in the bone marrow are spatially associated with blood vessels and are in intimate contact with nerve fibres. We used various combinations of markers to distinguish different cell types and found that the GFRα3-expressing cells expressed markers of nonmyelinating Schwann cells (e.g. GFAP, p75NTR, nestin). Analysis of bone marrow sections of Wnt1-reporter mice also demonstrated that they originate from the neural crest. Further characterisation using flow cytometry revealed that GFRα3 is expressed in a population of CD51+Sca1PDGFRα cells, reinforcing the notion that they are neural crest-derived, nonmyelinating Schwann cells. In conclusion, there is a close association between peripheral nerve terminals and a population of nonneuronal cells that express GFRα3 in the bone marrow. The nonneuronal cells have characteristics consistent with a neural crest-derived, nonmyelinating Schwann cell phenotype. Our findings provide a better understanding of the expression pattern of GFRα3 in the bone marrow microenvironment.

Keywords

Artemin GFRα3 Nonmyelinating Schwann cells Bone marrow Peripheral nervous system 

Notes

Acknowledgements

The authors acknowledge Professor Roberto Cappai and Phan Truong for generously providing us with tissue from C57BL/6 mice. Louise E. Purton was an NHMRC Senior Research Fellow.

Funding information

This work was supported by funding from the National Health and Medical Research Council and the Operational Infrastructure Support Program from the Victorian Government (to St. Vincent’s Institute).

Compliance with ethical standards

Ethical approval

All applicable international, national and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted. This article does not contain any studies with human participants performed by any of the authors. All experiments performed were in accordance with ethical standards of the University of Melbourne Animal Experimentation Ethics Committee, St. Vincent’s Health Animal Ethics Committee and the Animal Welfare Committee of Flinders University of South Australia.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Anatomy and NeuroscienceUniversity of MelbourneMelbourneAustralia
  2. 2.St. Vincent’s Institute of Medical Research and Department of Medicine at St. Vincent’s HospitalUniversity of MelbourneMelbourneAustralia
  3. 3.Department of Oncology and Metabolism and Mellanby Centre for Bone ResearchUniversity of SheffieldSheffieldUK
  4. 4.College of Medicine and Public Health, Center for NeuroscienceFlinders UniversityAdelaideAustralia

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