Tbx1 regulation of myogenic differentiation in the limb and cranial mesoderm

Department of Craniofacial Development, King's College London, Guy's Tower, London Bridge, United Kingdom.
Developmental Dynamics (Impact Factor: 2.38). 02/2007; 236(2):353-63. DOI: 10.1002/dvdy.21010
Source: PubMed


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.

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Available from: Philippa Francis-West, Jan 13, 2015
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    • "Hence, pharyngeal muscles require Tbx1 for robust bilateral specification. Head muscle defects in Tbx1 mutants are likely due to an intrinsic defect in the pharyngeal mesoderm (Dastjerdi et al. 2007), as well as to non-cell autonomous functions of Tbx1 in the endoderm and ectoderm (Arnold et al. 2006). Analyses of Tbx1 mutant embryos indicated that several fibroblast growth factor (FGF) family members expressed in these adjacent tissues were downregulated, demonstrating a role for Tbx1 and FGF signaling during head muscle development (Hu et al. 2004; Kelly et al. 2004; Knight et al. 2008; Vitelli et al. 2002; von Scheven et al. 2006). "
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    • "Another fascinating difference is that Mrf4, which is important for myogenic determination of limb and trunk progenitors, cannot fulfil the same role in the head [26]. It is now known that all the head muscles depend on Pitx2 and Tbx1, which are transcription factors that contain homeodomains, and which positively regulate one another as well as Myf5; Pitx2 and Tbx1 thus regulate the myogenic cascade [61–63]. Recently, it has been shown that only the extraocular eye muscle, and not other head muscles, depends on the presence of both Myf5 and Mrf4, whereby MyoD cannot compensate for their absence [64]. "
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