Tbx1 regulation of myogenic differentiation in the limb and cranial mesoderm

Akbar Dastjerdi, Lesley Robson, Rebecca Walker, Julia Hadley, Zhen Zhang, Marc Rodriguez-Niedenführ, Paris Ataliotis, Antonio Baldini, Peter Scambler, Philippa Francis-West

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)353-363
Number of pages11
JournalDevelopmental Dynamics
Volume236
Issue number2
DOIs
Publication statusPublished - Feb 2007

Keywords

  • Craniofacial mesoderm
  • DiGeorge syndrome
  • Limb
  • Muscle
  • T-box

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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    Dastjerdi, A., Robson, L., Walker, R., Hadley, J., Zhang, Z., Rodriguez-Niedenführ, M., Ataliotis, P., Baldini, A., Scambler, P., & Francis-West, P. (2007). Tbx1 regulation of myogenic differentiation in the limb and cranial mesoderm. Developmental Dynamics, 236(2), 353-363. https://doi.org/10.1002/dvdy.21010