Tbx1 regulation of myogenic differentiation in the limb and cranial mesoderm

Baylor College of Medicine, Houston, Texas, United States
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.

Download full-text


Available from: Philippa Francis-West, Jan 13, 2015
  • Source
    • "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). "

    Full-text · Dataset · Aug 2015
  • Source
    • "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]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Skeletal myogenesis has been and is currently under extensive study in both mammals and teleosts, with the latter providing a good model for skeletal myogenesis because of their flexible and conserved genome. Parallel investigations of muscle studies using both these models have strongly accelerated the advances in the field. However, when transferring the knowledge from one model to the other, it is important to take into account both their similarities and differences. The main difficulties in comparing mammals and teleosts arise from their different temporal development. Conserved aspects can be seen for muscle developmental origin and segmentation, and for the presence of multiple myogenic waves. Among the divergences, many fish have an indeterminate growth capacity throughout their entire life span, which is absent in mammals, thus implying different post-natal growth mechanisms. This review covers the current state of the art on myogenesis, with a focus on the most conserved and divergent aspects between mammals and teleosts.
    Full-text · Article · Mar 2014 · Cellular and Molecular Life Sciences CMLS
  • Source
    • "Whole-mount in situ hybridisation studies were carried out to E10.5, E11.5, E12.5 and E13.5 CD1 strain mouse embryos as previously described [88]. At E12.5 and E13.5 the palatal shelves were isolated to increase probe penetration. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Non-syndromic cleft lip/palate (NSCL/P) is a complex, frequent congenital malformation, determined by the interplay between genetic and environmental factors during embryonic development. Previous findings have appointed an aetiological overlap between NSCL/P and cancer, and alterations in similar biological pathways may underpin both conditions. Here, using a combination of transcriptomic profiling and functional approaches, we report that NSCL/P dental pulp stem cells exhibit dysregulation of a co-expressed gene network mainly associated with DNA double-strand break repair and cell cycle control (p = 2.88×10(-2)-5.02×10(-9)). This network included important genes for these cellular processes, such as BRCA1, RAD51, and MSH2, which are predicted to be regulated by transcription factor E2F1. Functional assays support these findings, revealing that NSCL/P cells accumulate DNA double-strand breaks upon exposure to H2O2. Furthermore, we show that E2f1, Brca1 and Rad51 are co-expressed in the developing embryonic orofacial primordia, and may act as a molecular hub playing a role in lip and palate morphogenesis. In conclusion, we show for the first time that cellular defences against DNA damage may take part in determining the susceptibility to NSCL/P. These results are in accordance with the hypothesis of aetiological overlap between this malformation and cancer, and suggest a new pathogenic mechanism for the disease.
    Full-text · Article · Jun 2013 · PLoS ONE
Show more