Tbx1 regulation of myogenic differentiation in the limb and cranial mesoderm

Authors

  • Akbar Dastjerdi,

    1. Department of Craniofacial Development, King's College London, Guy's Tower, London Bridge, United Kingdom
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  • Lesley Robson,

    1. Neuroscience Centre, Institute of Cell and Molecular Science, Barts and The London Queen Mary's School of Medicine and Dentistry, Whitechapel, London, United Kingdom
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  • Rebecca Walker,

    1. Department of Craniofacial Development, King's College London, Guy's Tower, London Bridge, United Kingdom
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  • Julia Hadley,

    1. Department of Craniofacial Development, King's College London, Guy's Tower, London Bridge, United Kingdom
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  • Zhen Zhang,

    1. Department of Pediatrics (Cardiology) and Program in Cardiovascular Sciences, Baylor College of Medicine, Houston, Texas
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  • Marc Rodriguez-Niedenführ,

    1. Department of Craniofacial Development, King's College London, Guy's Tower, London Bridge, United Kingdom
    Current affiliation:
    1. Molecular Oncology Laboratory, Cancer Research UK London Research Institute, 44 Lincolns Inn Fields, London, WC2A 3PX, UK
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  • Paris Ataliotis,

    1. Molecular Medicine Unit, The Institute of Child Health, London, United Kingdom
    Current affiliation:
    1. St George's, University of London, Division of Basic Medical Sciences, Cranmer Terrace, London SW17 ORE, UK
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  • Antonio Baldini,

    1. Department of Pediatrics (Cardiology) and Program in Cardiovascular Sciences, Baylor College of Medicine, Houston, Texas
    Current affiliation:
    1. Alkek Institute of Biosciences and Technology, Texas, A&M System Health Science Center, 2121 W. Holcombe Houston, TX 77030
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  • Peter Scambler,

    1. Molecular Medicine Unit, The Institute of Child Health, London, United Kingdom
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  • Philippa Francis-West

    Corresponding author
    1. Department of Craniofacial Development, King's College London, Guy's Tower, London Bridge, United Kingdom
    • Department of Craniofacial Development, King's College London, Guy's Tower, floor 28, London Bridge, SE1 9RT, UK
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Abstract

The T-box transcription factor Tbx1 has been implicated in DiGeorge syndrome, the most frequent syndrome due to a chromosomal deletion. Gene inactivation of Tbx1 in mice results in craniofacial and branchial arch defects, including myogenic defects in the first and second branchial arches. A T-box binding site has been identified in the Xenopus Myf5 promoter, and in other species, T-box genes have been implicated in myogenic fate. Here we analyze Tbx1 expression in the developing chick embryo relating its expression to the onset of myogenic differentiation and cellular fate within the craniofacial mesoderm. We show that Tbx1 is expressed before capsulin, the first known marker of branchial arch 1 and 2 muscles. We also show that, as in the mouse, Tbx1 is expressed in endothelial cells, another mesodermal derivative, and, therefore, Tbx1 alone cannot specify the myogenic lineage. In addition, Tbx1 expression was identified in both chick and mouse limb myogenic cells, initially being restricted to the dorsal muscle mass, but in contrast, to the head, here Tbx1 is expressed after the onset of myogenic commitment. Functional studies revealed that loss of Tbx1 function reduces the number of myocytes in the head and limb, whereas increasing Tbx1 activity has the converse effect. Finally, analysis of the Tbx1-mesoderm-specific knockout mouse demonstrated the cell autonomous requirement for Tbx1 during myocyte development in the cranial mesoderm. Developmental Dynamics 236:353–363, 2007. © 2006 Wiley-Liss, Inc.

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