Neural crest origins of the neck and shoulder.
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.
Matsuoka
Toshiyuki
T
Wolfson Institute for Biomedical Research, University College London, Gower Street, London WC1E 6BT, UK.
Ahlberg
Per E
PE
Kessaris
Nicoletta
N
Iannarelli
Palma
P
Dennehy
Ulla
U
Richardson
William D
WD
McMahon
Andrew P
AP
Koentges
Georgy
G
D000663:Amphibians / Q000196:embryology; D000818:Animals; D005075:Biological Evolution; D001846:Bone Development; D019070:Cell Lineage; D002465:Cell Movement; D005580:Fossils; D006801:Humans; D008322:Mammals / Q000196:embryology; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009333:Neck / Q000196:embryology* / Q000473:pathology; D009432:Neural Crest / Q000166:cytology / Q000378:metabolism*; D012782:Shoulder / Q000196:embryology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism