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Cellular and molecular investigations into the development of the pectoral girdle
Authors:Valasek Petr  Theis Susanne  DeLaurier April  Hinits Yaniv  Luke Graham N  Otto Anthony M  Minchin James  He Liwen  Christ Bodo  Brooks Gavin  Sang Helen  Evans Darrell J  Logan Malcolm  Huang Ruijin  Patel Ketan
Affiliation:aSchool of Biological Sciences and Institute for Cardiovascular and Metabolic Research (ICMR), University of Reading, UK;bInstitute of Anatomy, First Faculty of Medicine, Charles University in Prague, Czech Republic;cInstitute of Anatomy, University of Bonn, Germany;dInstitute of Anatomy and Cell Biology, University of Freiburg, Germany;eInstitute of Neuroscience, University of Oregon, OR, USA;fRandall Division of Cell and Molecular Biophysics, King's College London-Guy's Campus, UK;gCell & Molecular Physiology, University of North Carolina at Chapel Hill, USA;hZhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, China;iRoslin Institute and R(D)SVS, University of Edinburgh, Midlothian, UK;jBrighton and Sussex Medical School, University of Sussex, Falmer, UK;kDivision of Developmental Biology, National Institute for Medical Research, Mill Hill, London, UK
Abstract:The forelimbs of higher vertebrates are composed of two portions: the appendicular region (stylopod, zeugopod and autopod) and the less prominent proximal girdle elements (scapula and clavicle) that brace the limb to the main trunk axis.We show that the formation of the muscles of the proximal limb occurs through two distinct mechanisms. The more superficial girdle muscles (pectoral and latissimus dorsi) develop by the “In–Out” mechanism whereby migration of myogenic cells from the somites into the limb bud is followed by their extension from the proximal limb bud out onto the thorax. In contrast, the deeper girdle muscles (e.g. rhomboideus profundus and serratus anterior) are induced by the forelimb field which promotes myotomal extension directly from the somites. Tbx5 inactivation demonstrated its requirement for the development of all forelimb elements which include the skeletal elements, proximal and distal muscles as well as the sternum in mammals and the cleithrum of fish. Intriguingly, the formation of the diaphragm musculature is also dependent on the Tbx5 programme. These observations challenge our classical views of the boundary between limb and trunk tissues. We suggest that significant structures located in the body should be considered as components of the forelimb.
Keywords:Forelimb   Shoulder girdle   Muscle   Tbx5   Diaphragm   Sternum
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