Evolution of the hypoxia-sensitive cells involved in amniote respiratory reflexes

  1. Dorit Hockman
  2. Alan J Burns
  3. Gerhard Schlosser
  4. Keith P Gates
  5. Benjamin Jevans
  6. Alessandro Mongera
  7. Shannon Fisher
  8. Gokhan Unlu
  9. Ela W Knapik
  10. Charles K Kaufman
  11. Christian Mosimann
  12. Leonard I Zon
  13. Joseph J Lancman
  14. P Duc S Dong
  15. Heiko Lickert
  16. Abigail S Tucker
  17. Clare VH Baker  Is a corresponding author
  1. University of Oxford, United Kingdom
  2. UCL Great Ormond Street Institute of Child Health, United Kingdom
  3. National University of Ireland, Ireland
  4. Sanford Burnham Prebys Medical Discovery Institute, United States
  5. University of California, California NanoSystem Institute, United States
  6. Boston University School of Medicine, United States
  7. Vanderbilt University Medical Center, United States
  8. Washington University School of Medicine, United States
  9. University of Zürich, Switzerland
  10. Howard Hughes Medical Institute, Harvard Medical School, United States
  11. Helmholtz Zentrum München, Germany
  12. King's College London, United Kingdom
  13. University of Cambridge, United Kingdom

Abstract

The evolutionary origins of the hypoxia-sensitive cells that trigger amniote respiratory reflexes - carotid body glomus cells, and 'pulmonary neuroendocrine cells' (PNECs) - are obscure. Homology has been proposed between glomus cells, which are neural crest-derived, and the hypoxia-sensitive 'neuroepithelial cells' (NECs) of fish gills, whose embryonic origin is unknown. NECs have also been likened to PNECs, which differentiate in situ within lung airway epithelia. Using genetic lineage-tracing and neural crest-deficient mutants in zebrafish, and physical fate-mapping in frog and lamprey, we find that NECs are not neural crest-derived, but endoderm-derived, like PNECs, whose endodermal origin we confirm. We discover neural crest-derived catecholaminergic cells associated with zebrafish pharyngeal arch blood vessels, and propose a new model for amniote hypoxia-sensitive cell evolution: endoderm-derived NECs were retained as PNECs, while the carotid body evolved via the aggregation of neural crest-derived catecholaminergic (chromaffin) cells already associated with blood vessels in anamniote pharyngeal arches.

Article and author information

Author details

  1. Dorit Hockman

    Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Alan J Burns

    Stem Cells and Regenerative Medicine, UCL Great Ormond Street Institute of Child Health, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Gerhard Schlosser

    School of Natural Sciences, National University of Ireland, Galway, Ireland
    Competing interests
    The authors declare that no competing interests exist.
  4. Keith P Gates

    Human Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Benjamin Jevans

    Stem Cells and Regenerative Medicine, UCL Great Ormond Street Institute of Child Health, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Alessandro Mongera

    Department of Mechanical Engineering, University of California, California NanoSystem Institute, Santa Barbara, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Shannon Fisher

    Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Gokhan Unlu

    Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Ela W Knapik

    Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Charles K Kaufman

    Department of Medicine, Division of Oncology, Washington University School of Medicine, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Christian Mosimann

    Institute of Molecular Life Sciences, University of Zürich, Zürich, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  12. Leonard I Zon

    Children's Hospital Boston, Howard Hughes Medical Institute, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0860-926X
  13. Joseph J Lancman

    Human Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. P Duc S Dong

    Human Genetics Program, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Heiko Lickert

    Institute of Diabetes and Regeneration Research, Helmholtz Zentrum München, Neuherberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  16. Abigail S Tucker

    Department of Craniofacial Development and Stem Cell Biology, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  17. Clare VH Baker

    Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
    For correspondence
    cvhb1@cam.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4434-3107

Funding

Wellcome (086804/Z/08/Z)

  • Dorit Hockman

Wellcome (102889/Z/13/Z)

  • Abigail S Tucker

National Institute of Dental and Craniofacial Research (R01-DE018477)

  • Ela W Knapik

National Institute of Diabetes and Digestive and Kidney Diseases (1DP2DK098092)

  • P Duc S Dong

Human Frontier Science Program (Long-Term Fellowship)

  • Christian Mosimann

Helmholtz-Gemeinschaft (Helmholtz Portfolio Theme 'Metabolic Dysfunction and Common Disease')

  • Heiko Lickert

Helmoltz Alliance (Imaging and Curing Environmental Metabolic Disease)

  • Heiko Lickert

German Center for Diabetes Research

  • Heiko Lickert

National Institutes of Health (R01-HL092217)

  • Ela W Knapik

National Institute of Dental and Craniofacial Research (R21-DE021509)

  • Shannon Fisher

Zebrafish Initiative of the Vanderbilt University Venture Capital Fund

  • Ela W Knapik

Vanderbilt International Scholar Program (Graduate Student Scholarship)

  • Gokhan Unlu

Swiss National Science Foundation (Advanced Postdoctoral Fellowship and Professorship)

  • Christian Mosimann

Cambridge Trusts (Graduate Student Scholarship)

  • Dorit Hockman

Cambridge Philosophical Society (Graduate Student Scholarship)

  • Dorit Hockman

Oppenheimer Memorial Trust (Graduate Student Scholarship)

  • Dorit Hockman

Trinity College Oxford (Junior Research Fellowship)

  • Dorit Hockman

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Experiments using Tg(-4.9sox10:creERT2);Tg(βactin:loxP-SuperStop-loxP-DsRed) zebrafish were conducted in compliance with the regulations of the Regierungspräsidium Tübingen and the Max Planck Society. Experiments using all other zebrafish lines were conducted according to protocols approved by the Institutional Animal Care and Use Committees in facilities accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC).Experiments using Xenopus laevis were conducted in accordance with the UK Animals (Scientific Procedures) Act 1986, with appropriate personal and project licences in place where necessary.Experiments using sea lamprey (Petromyzon marinus) were conducted according to protocols approved by the California Institute of Technology Institutional Animal Care and Use Committee.Experiments using transgenic mice were conducted in accordance with the UK Animals (Scientific Procedures) Act 1986, with appropriate personal and project licences in place.Experiments using chicken (Gallus gallus domesticus) embryos were conducted in accordance with the UK Animals (Scientific Procedures) Act 1986, with appropriate personal and project licences in place where necessary.

Reviewing Editor

  1. Robb Krumlauf, Stowers Institute for Medical Research, United States

Publication history

  1. Received: September 3, 2016
  2. Accepted: April 7, 2017
  3. Accepted Manuscript published: April 7, 2017 (version 1)
  4. Accepted Manuscript updated: April 11, 2017 (version 2)
  5. Version of Record published: May 19, 2017 (version 3)

Copyright

© 2017, Hockman et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,760
    Page views
  • 618
    Downloads
  • 41
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Dorit Hockman
  2. Alan J Burns
  3. Gerhard Schlosser
  4. Keith P Gates
  5. Benjamin Jevans
  6. Alessandro Mongera
  7. Shannon Fisher
  8. Gokhan Unlu
  9. Ela W Knapik
  10. Charles K Kaufman
  11. Christian Mosimann
  12. Leonard I Zon
  13. Joseph J Lancman
  14. P Duc S Dong
  15. Heiko Lickert
  16. Abigail S Tucker
  17. Clare VH Baker
(2017)
Evolution of the hypoxia-sensitive cells involved in amniote respiratory reflexes
eLife 6:e21231.
https://doi.org/10.7554/eLife.21231
  1. Further reading

Further reading

    1. Developmental Biology
    2. Neuroscience
    Tanya L Brown, Emma C Horton ... Jeffrey P Rasmussen
    Research Article Updated

    Touch system function requires precise interactions between specialized skin cells and somatosensory axons, as exemplified by the vertebrate mechanosensory Merkel cell-neurite complex. Development and patterning of Merkel cells and associated neurites during skin organogenesis remain poorly understood, partly due to the in utero development of mammalian embryos. Here, we discover Merkel cells in the zebrafish epidermis and identify Atonal homolog 1a (Atoh1a) as a marker of zebrafish Merkel cells. We show that zebrafish Merkel cells derive from basal keratinocytes, express neurosecretory and mechanosensory machinery, extend actin-rich microvilli, and complex with somatosensory axons, all hallmarks of mammalian Merkel cells. Merkel cells populate all major adult skin compartments, with region-specific densities and distribution patterns. In vivo photoconversion reveals that Merkel cells undergo steady loss and replenishment during skin homeostasis. Merkel cells develop concomitant with dermal appendages along the trunk and loss of Ectodysplasin signaling, which prevents dermal appendage formation, reduces Merkel cell density by affecting cell differentiation. By contrast, altering dermal appendage morphology changes the distribution, but not density, of Merkel cells. Overall, our studies provide insights into touch system maturation during skin organogenesis and establish zebrafish as an experimentally accessible in vivo model for the study of Merkel cell biology.

    1. Developmental Biology
    Bavat Bornstein, Lia Heinemann-Yerushalmi ... Elazar Zelzer
    Tools and Resources

    The proprioceptive system is essential for the control of coordinated movement, posture and skeletal integrity. The sense of proprioception is produced in the brain using peripheral sensory input from receptors such as the muscle spindle, which detects changes in the length of skeletal muscles. Despite its importance, the molecular composition of the muscle spindle is largely unknown. In this study, we generated comprehensive transcriptomic and proteomic datasets of the entire muscle spindle isolated from the murine deep masseter muscle. We then associated differentially expressed genes with the various tissues composing the spindle using bioinformatic analysis. Immunostaining verified these predictions, thus establishing new markers for the different spindle tissues. Utilizing these markers, we identified the differentiation stages the spindle capsule cells undergo during development. Together, these findings provide comprehensive molecular characterization of the intact spindle as well as new tools to study its development and function in health and disease.