Nature 436, 347-355 (21 July 2005) | doi:10.1038/nature03837; Received 13 September 2004; Accepted 20 May 2005

Neural crest origins of the neck and shoulder

Toshiyuki Matsuoka1,2,6, Per E. Ahlberg4,6, Nicoletta Kessaris1, Palma Iannarelli1, Ulla Dennehy1, William D. Richardson1,3, Andrew P. McMahon5 & Georgy Koentges1,2,3

  1. Wolfson Institute for Biomedical Research,
  2. Laboratory of Functional Genomics,
  3. Department of Biology, University College London, Gower Street, London WC1E 6BT, UK
  4. Subdepartment of Evolutionary Organismal Biology, Department of Physiology and Developmental Biology, Uppsala University, Norbyvägen 18 A, 752 36 Uppsala, Sweden
  5. Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts 02138, USA
  6. *These authors contributed equally to this work

Correspondence to: Georgy Koentges1,2,3 Correspondence and requests for materials should be addressed to G.K. (Email:


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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