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Neural crest origins of the neck and shoulder

Nature volume 436, pages 347–355 (2005)Cite this article

Abstract

The neck and shoulder region of vertebrates has undergone a complex evolutionary history. To identify its underlying mechanisms we map the destinations of embryonic neural crest and mesodermal stem cells using Cre-recombinase-mediated transgenesis. The single-cell resolution of this genetic labelling reveals cryptic cell boundaries traversing the seemingly homogeneous skeleton of the neck and shoulders. Within this assembly of bones and muscles we discern a precise code of connectivity that mesenchymal stem cells of both neural crest and mesodermal origin obey as they form muscle scaffolds. The neural crest anchors the head onto the anterior lining of the shoulder girdle, while a Hox-gene-controlled mesoderm links trunk muscles to the posterior neck and shoulder skeleton. The skeleton that we identify as neural crest-derived is specifically affected in human Klippel–Feil syndrome, Sprengel's deformity and Arnold–Chiari I/II malformation, providing insights into their likely aetiology. We identify genes involved in the cellular modularity of the neck and shoulder skeleton and propose a new method for determining skeletal homologies that is based on muscle attachments. This has allowed us to trace the whereabouts of the cleithrum, the major shoulder bone of extinct land vertebrate ancestors, which seems to survive as the scapular spine in living mammals.

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Figure 1: Conservation of muscle scaffolds and diversity of shoulder ossification patterns.
Figure 2: Genetic lineage labelling of PONC and somitic mesoderm in the neck.
Figure 3: Neural crest and somitic mesodermal origins of the neck.
Figure 4: Dual neural crest and mesodermal origins of the endochondral shoulder girdle.
Figure 5: The dual architecture of the clavicle: cell population boundaries coincide with muscle attachments and not with ossification modes.
Figure 7: Muscle scaffolds in fossils.
Figure 6: Pathological flexibility of PONC differentiation.

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Acknowledgements

We thank A. Lumsden for help with a complex manuscript; P. Soriano and S. Orkin for providing Cre reporters; and A. West, G. Felsenfeld and J. Green for advice on insulators and plasmids. This work was funded by the BBSRC (G.K., P.E.A.), the Wellcome Trust (G.K., W.D.R.), the MRC UK (W.D.R.), the Swedish Research Council (P.E.A.), the NIH (A.P.M.) and WIBR-UCL (G.K.). G.K. and T.M. were long-term postdoctoral fellows of HFSPO. G.K. thanks S. Moncada for support in establishing a new laboratory.Author Contributions T.M. and P.E.A. contributed equally to this work.

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Author notes

  1. Toshiyuki Matsuoka and Per E. Ahlberg: *These authors contributed equally to this work

Authors and Affiliations

  1. Wolfson Institute for Biomedical Research,

    Toshiyuki Matsuoka, Nicoletta Kessaris, Palma Iannarelli, Ulla Dennehy, William D. Richardson & Georgy Koentges

  2. Laboratory of Functional Genomics,

    Toshiyuki Matsuoka & Georgy Koentges

  3. Department of Biology, University College London, Gower Street, WC1E 6BT, London, UK

    William D. Richardson & Georgy Koentges

  4. Subdepartment of Evolutionary Organismal Biology, Department of Physiology and Developmental Biology, Uppsala University, Norbyvägen 18 A, 752 36, Uppsala, Sweden

    Per E. Ahlberg

  5. Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Massachusetts, 02138, Cambridge, USA

    Andrew P. McMahon

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Correspondence to Georgy Koentges.

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Supplementary information

Supplementary Figure S1

This figure details mouse mutant neck phenotypes. (PDF 147 kb)

Supplementary Methods S1

This file contains Supplementary Methods and analysis. (PDF 343 kb)

Supplemental Methods S2

New methodology for determining neck/shoulder homologies. Also includes additional references. (PDF 46 kb)

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Matsuoka, T., Ahlberg, P., Kessaris, N. et al. Neural crest origins of the neck and shoulder. Nature 436, 347–355 (2005). https://doi.org/10.1038/nature03837

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