Article | Published:

Meckel’s cartilage breakdown offers clues to mammalian middle ear evolution

Nature Ecology & Evolution volume 1, Article number: 0093 (2017) | Download Citation

Abstract

A key transformation in mammalian ear evolution was incorporation of the primary jaw joint of premammalian synapsids into the definitive mammalian middle ear of living mammals. This evolutionary transition occurred in two steps, starting with a partial or ‘transitional’ mammalian middle ear in which the ectotympanic and malleus were still connected to the mandible by an ossified Meckel’s cartilage (MC), as observed in many Mesozoic mammals. This was followed by MC breakdown, freeing the ectotympanic and the malleus from the mandible and creating the definitive mammalian middle ear. Here we report new findings on the role of chondroclasts in MC breakdown, shedding light on how therian mammals lost the part of the MC connecting the ear to the jaw. Genetic or pharmacological loss of clast cells in mice and opossums leads to persistence of embryonic MC beyond juvenile stages, with MC ossification in mutant mice. The persistent MC causes a distinctive groove on the postnatal mouse dentary. This morphology phenocopies the ossified MC and Meckelian groove observed in Mesozoic mammals. Clast cell recruitment to MC is not observed in reptiles, where MC persists as a cartilaginous structure. We hypothesize that ossification of MC is an ancestral feature of mammaliaforms, and that a shift in the timing of clast cell recruitment to MC prior to its ossification is a key developmental mechanism for the evolution of the definitive mammalian middle ear in extant therians.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    & in The Evolutionary Biology of Hearing (eds Webster, D. B., Fay, R. R. & Popper, A. N.) 587–614 (Springer, 1992).

  2. 2.

    Coevolution of the mammalian middle ear and neocortex. Science 273, 651–654 (1996).

  3. 3.

    Transformation and diversification in early mammal evolution. Nature 450, 1011–1019 (2007).

  4. 4.

    & in From Clone to Bone: The Synergy of Morphological and Molecular Tools in Palaeobiology (eds Asher, R. J. & Müller, J.) 207–229 (Cambridge Univ. Press, 2012).

  5. 5.

    & Evolution of the mammalian middle ear: a historical review. J. Anat. 228, 270–283 (2016).

  6. 6.

    Developmental patterns in Mesozoic evolution of mammal ears. Annu. Rev. Ecol. Evol. Syst. 42, 355–380 (2011).

  7. 7.

    , , & The ossified Meckel’s cartilage and internal groove in Mesozoic mammaliaforms: implications to origin of the definitive mammalian middle ear. Zool. J. Linn. Soc. 138, 431–448 (2003).

  8. 8.

    , , , & Evolutionary development of the middle ear in Mesozoic therian mammals. Science 326, 278–281 (2009).

  9. 9.

    & History of studies on mammalian middle ear evolution: a comparative morphological and developmental biology perspective. J. Exp. Zool. B 314, 417–433 (2010).

  10. 10.

    et al. Meckel’s cartilage: discovery, embryology and evolution. J. Oral Biosci. 52, 125–135 (2010).

  11. 11.

    , & Evolution of the mammalian middle ear and jaw: adaptations and novel structures. J. Anat. 222, 147–160 (2013).

  12. 12.

    , , , & Ontogenetic and phylogenetic transformations of the ear ossicles in marsupial mammals. J. Morphol. 251, 219–238 (2002).

  13. 13.

    & Joint formation in the middle ear: lessons from the mouse and guinea pig. Dev. Dyn. 235, 1326–1333 (2006).

  14. 14.

    & Fgf and Bmp signals repress the expression of Bapx1 in the mandibular mesenchyme and control the position of the developing jaw joint. Dev. Biol. 266, 138–150 (2004).

  15. 15.

    , & Transitional mammalian middle ear from a new Cretaceous Jehol eutriconodont. Nature 472, 181–185 (2011).

  16. 16.

    , , , & Mandibular and dental characteristics of Late Triassic mammaliaform Haramiyavia and their ramifications for basal mammal evolution. Proc. Natl Acad. Sci. USA 112, E7101–E7109 (2015).

  17. 17.

    & Morphology and diversity of the mandibular symphysis of archosauriforms. Geol. Soc. Lond. Spec. Publ. 379, 555–571 (2013).

  18. 18.

    Craniofacial development in marsupial mammals: developmental origins of evolutionary change. Dev. Dyn. 235, 1181–1193 (2006).

  19. 19.

    Die Reichertsche theorie: (Hammer-, amboss-und kieferfrage). Arch. Anat. Suppl. 1912, 1–416 (1913).

  20. 20.

    Bones and Cartilage: Developmental and Evolutionary Skeletal Biology. (Academic, 2015).

  21. 21.

    et al. Chondroclasts are mature osteoclasts which are capable of cartilage matrix resorption. Virchows Arch. 461, 205–210 (2012).

  22. 22.

    & Chondroclasts and endothelial cells collaborate in the process of cartilage resorption. Anat. Rec. 233, 504–514 (1992).

  23. 23.

    et al. c-Fos: a key regulator of osteoclast-macrophage lineage determination and bone remodeling. Science 266, 443–448 (1994).

  24. 24.

    et al. Fos plays an essential role in the upregulation of RANK expression in osteoclast precursors within the bone microenvironment. J. Cell Sci. 125, 2910–2917 (2012).

  25. 25.

    , , & Biochemical and molecular mechanisms of action of bisphosphonates. Bone 49, 34–41 (2011).

  26. 26.

    et al. A Cretaceous eutriconodont and integument evolution in early mammals. Nature 526, 380–384 (2015).

  27. 27.

    Written in stone: fossils, genes and evo–devo. Nat. Rev. Genet. 8, 911–920 (2007).

  28. 28.

    et al. A new developmental mechanism for the separation of the mammalian middle ear ossicles from the jaw. Proc. R. Soc. B. (in the press).

  29. 29.

    Role of matrix metalloproteinases in extracellular matrix disintegration of Meckel’s cartilage in mice. J. Oral Biosci. 52, 143–149 (2010).

  30. 30.

    , , , & Hypertrophic chondrocytes can become osteoblasts and osteocytes in endochondral bone formation. Proc. Natl Acad. Sci. USA 111, 12097–12102 (2014).

  31. 31.

    et al. New roles for osteoclasts in bone. Ann. NY Acad. Sci. 1116, 245–254 (2007).

  32. 32.

    et al. Immunolocalization of receptor activator of nuclear factor-kappaB ligand (RANKL) and osteoprotegerin (OPG) in Meckel’s cartilage compared with developing endochondral bones in mice. J. Anat. 207, 325–337 (2005).

  33. 33.

    , , & Enhanced BMP signaling prevents degeneration and leads to endochondral ossification of Meckel′s cartilage in mice. Dev. Biol. 381, 301–311 (2013).

  34. 34.

    von Baer’s law for the ages: lost and found principles of developmental evolution. Trends Genet. 29, 712–722 (2013).

  35. 35.

    et al. Bone and haematopoietic defects in mice lacking c-fos. Nature 360, 741–745 (1992).

  36. 36.

    , & Complex patterns of tooth replacement revealed in the fruit bat (Eidolon helvum). J. Anat. (2016). E-pub ahead of print.

  37. 37.

    et al. Neural crest-mediated bone resorption is a determinant of species-specific jaw length. Dev. Biol. 408, 151–163 (2015).

Download references

Acknowledgements

We thank C. Healy (KCL) and L. Yin (UIUC) for support with μCT, E. Popa (King’s College London, KCL) for assistance in processing tissue, J. M. Fons (KCL) for injection of newborn mice, A. Neander (University of Chicago) for graphics assistance, A. Grigoriadis (KCL) for supplying the c-Fos mutant mice and in situ probes, and J. Turner and F. Decarpentrie (Francis Crick Institute) for supplying opossum pups. For this project, N.A. was supported by the Leverhulme Trust (RPG-2013-070) and the Wellcome Trust (102889/Z/13/Z) and NSF/EDEN Research Exchange Grant (IOS 0955517) A.S.T. is funded by the Wellcome Trust (102889/Z/13/Z). D.J.U. was supported by a NSF Graduate Research Fellowship (2013136301) and K.E.S. by a Doctoral Dissertation Improvement Grant (1406802).

Author information

Affiliations

  1. Department of Craniofacial Development and Stem Cell Biology, King’s College London, Floor 27, Guy’s Tower, Guy’s Hospital, London SE1 9RT, UK

    • Neal Anthwal
    •  & Abigail S. Tucker
  2. School of Integrative Biology, 505 South Goodwin Avenue, University of Illinois, Urbana, Illinois 61801, USA

    • Daniel J. Urban
    •  & Karen E. Sears
  3. Department of Organismal Biology and Anatomy, University of Chicago, Chicago, Illinois 60637, USA

    • Zhe-Xi Luo
  4. Carl Woese Institute for Genomic Biology, 1206 West Gregory Drive, University of Illinois, Urbana Illinois 61801, USA

    • Karen E. Sears

Authors

  1. Search for Neal Anthwal in:

  2. Search for Daniel J. Urban in:

  3. Search for Zhe-Xi Luo in:

  4. Search for Karen E. Sears in:

  5. Search for Abigail S. Tucker in:

Contributions

N.A. and A.S.T. conceived and designed the project. N.A. carried out mouse and reptile experimental work; K.E.S. and D.J.U. carried out opossum experimental work. Z.X.L. carried out fossil analysis. N.A. wrote the manuscript with A.S.T. A.S.T., Z.X.L, K.E.S. and D.J.U. critically appraised and edited the manuscript. All authors read and approved the manuscript before submission.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Abigail S. Tucker.

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    Supplementary Figures 1–6; Supplementary Discussion

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/s41559-017-0093