Lesley Robson

Queen Mary, University of London, Londinium, England, United Kingdom

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Publications (8)32.89 Total impact

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    ABSTRACT: Wnt signaling has been implicated in somite, limb, and branchial arch myogenesis but the mechanisms and roles are not clear. We now show that Wnt signaling via Lef1 acts to regulate the number of premyogenic cells in somites but does not regulate myogenic initiation in the limb bud or maintenance in the first or second branchial arch. We have also analysed the function and regulation of a putative downstream transcriptional target of canonical Wnt signaling, Pitx2. We show that loss-of-function of Pitx2 decreases the number of myogenic cells in the somite, whereas overexpression increases myocyte number particularly in the epaxial region of the myotome. Increased numbers of mitotic cells were observed following overexpression of Pitx2 or an activated form of Lef1, suggesting an effect on cell proliferation. In addition, we show that Pitx2 expression is regulated by canonical Wnt signaling in the epaxial somite and second branchial arch, but not in the limb or the first branchial arch. These results suggest that Wnt/Lef1 signaling regulates epaxial myogenesis via Pitx2 but that this link is uncoupled in other regions of the body, emphasizing the unique molecular networks that control the development of various muscles in vertebrates.
    Developmental Biology 10/2009; 337(2):211-9. · 3.87 Impact Factor
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    ABSTRACT: The compounds diethyl-N-carbazolylmethylphosphonate 1 and diethyl-2-oxymethylphosphonate carbazole 2 have been synthesised and characterized by a range of techniques including NMR, absorption and emission spectroscopy, infrared, and mass spectroscopy. Compound 1 forms a 2:1 complex 3 with calcium nitrate and the single crystal X-ray diffraction structure of 3 is described. Titrations of 1 with Zn2+ and Ca2+ in ethanol reveal that the intrinsic fluorescence is only slightly perturbed in the presence of these metal ions in micromolar ethanol solutions. Compounds 1 and 2 are readily taken up and visualized in L929 fibrosarcoma and DRG (Dorsal root ganglia) cell lines.
    Polyhedron 01/2009; 28(18):4115-4121. · 1.81 Impact Factor
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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 03/2007; 236(2):353-63. · 2.59 Impact Factor
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    ABSTRACT: The limb musculature arises by delamination of premyogenic cells from the lateral dermomyotome. Initially the cells express Pax3 but, upon entering the limb bud, they switch on the expression of MyoD and Myf5 and undergo terminal differentiation into slow or fast fibres, which have distinct contractile properties that determine how a muscle will function. In the chick, the premyogenic cells express the Wnt antagonist Sfrp2, which is downregulated as the cells differentiate, suggesting that Wnts might regulate myogenic differentiation. Here, we have investigated the role of Wnt signalling during myogenic differentiation in the developing chick wing bud by gain- and loss-of-function studies in vitro and in vivo. We show that Wnt signalling changes the number of fast and/or slow fibres. For example, in vivo, Wnt11 decreases and increases the number of slow and fast fibres, respectively, whereas overexpression of Wnt5a or a dominant-negative Wnt11 protein have the opposite effect. The latter shows that endogenous Wnt11 signalling determines the number of fast and slow myocytes. The distinct effects of Wnt5a and Wnt11 are consistent with their different expression patterns, which correlate with the ultimate distribution of slow and fast fibres in the wing. Overexpression of activated calmodulin kinase II mimics the effect of Wnt5a, suggesting that it uses this pathway. Finally, we show that overexpression of the Wnt antagonist Sfrp2 and DeltaLef1 reduces the number of myocytes. In Sfrp2-infected limbs, the number of Pax3 expressing cells was increased, suggesting that Sfrp2 blocks myogenic differentiation. Therefore, Wnt signalling modulates both the number of terminally differentiated myogenic cells and the intricate slow/fast patterning of the limb musculature.
    Development 09/2003; 130(15):3503-14. · 6.21 Impact Factor
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    ABSTRACT: The molecular cascades that control craniofacial development have until recently been little understood. The paucity of data that exists has in part been due to the complexity of the head, which is the most intricate regions of the body. However, the generation of mouse mutants and the identification of gene mutations that cause human craniofacial syndromes, together with classical embryological approaches in other species, have given significant insight into how the head develops. These studies have emphasized how unique the head actually is, with each individual part governed by a distinct set of signalling interactions, again demonstrating the complexity of this region of the body. This review discussed the tissue and molecular interactions that control each region of the head. The processes that control neural tube closure together with correct development of the skull, midline patterning, neural crest generation and migration, outgrowth, patterning, and differentiation of the facial primordia and the branchial arches are thus discussed. Defects in these processes result in a number of human syndromes such as exencephaly, holoprosencephaly, musculoskeletal dysplasias, first arch syndromes such as Riegers and Treacher-Collins syndrome, and neural crest dysplasias such as DiGeorge syndrome. Our current knowledge of the genes responsible for these human syndromes together with how the head develops, is rapidly advancing so that we will soon understand the complex set of molecular and tissue interactions that build a head.
    Advances in anatomy, embryology, and cell biology 02/2003; 169:III-VI, 1-138. · 9.80 Impact Factor
  • Journal of Anatomy 12/2002; 201(5):421. · 2.36 Impact Factor
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    ABSTRACT: The Wnt genes are known to play fundamental roles during patterning and development of a number of embryonic structures. Receptors for Wnts are members of the Frizzled family of proteins containing a cysteine-rich domain (CRD) that binds the Wnt protein. Recently several secreted frizzled-related proteins (Sfrps) that also contain a CRD have been identified and some of these can both bind and antagonise Wnt proteins. In this paper we report the expression patterns of the chick homologues of Frzb, a known Wnt antagonist, and Sfrp-2. Both genes are expressed in areas where Wnts are known to play a role in development, including the neural tube, myotome, cartilage, and sites of epithelial-mesenchymal interactions. Initially, Sfrp-2 and Frzb are expressed in overlapping areas in the neural plate and neural tube, whereas later, they have distinct patterns. In particular Sfrp-2 is associated with myogenesis while Frzb is associated with chondrogenesis, suggesting that they play different roles during development. Finally, we have used the early Xenopus embryo as an in vivo assay to show that Sfrp-2, like Frzb, is a Wnt antagonist. These results suggest that Sfrp-2 and Frzb may function in the developing embryo by modulating Wnt signalling.
    Developmental Biology 03/2000; 218(2):183-98. · 3.87 Impact Factor
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    ABSTRACT: Development of the musculature in chick limbs involves tissue and cellular patterning. Patterning at the tissue level leads to the precise arrangement of specific muscles; at the cellular level patterning gives rise to the fibre type diversity in muscles. Although the data suggests that the information controlling muscle patterning is localised within the limb mesenchyme and not in the somitic myogenic precursor cells themselves, the mechanisms underlying muscle organisation have still to be elucidated. The anterior-posterior axis of the limb is specified by a group of cells in the posterior region of the limb mesenchyme, called the zone of polarizing activity (ZPA). When polarizing-region cells are grafted to the anterior margin of the bud, they cause mirror-image digit duplications to be produced. The effect of ZPA grafts can be reproduced by application of retinoic acid (RA) beads and by grafting sonic hedgehog (SHH)-expressing cells to the anterior margin of the limb. Although most previous studies have looked at changes of the skeletal patterning, ZPA and RA also affect muscle patterning. In this report, we investigated the role of SHH in tissue and cellular patterning of forearm wing muscles. Ectopic application of a localised source of SHH to the anterior margin of the wing, leading to complete digit duplication, is able to transform anterior forearm muscles into muscles with a posterior identity. Moreover, the ectopic source of SHH induces a mirror image duplication of the normal posterior muscles fibre types in the new posterior muscles. The reorganisation of the slow fibres can be detected before muscle mass cleavage has started; suggesting that the appropriate fibre type arrangement is in place before the splitting process can be observed.
    Mechanisms of Development 05/1999; 82(1-2):151-63. · 2.38 Impact Factor

Publication Stats

327 Citations
32.89 Total Impact Points

Institutions

  • 2000–2009
    • Queen Mary, University of London
      Londinium, England, United Kingdom
  • 1999
    • Collège de France
      Lutetia Parisorum, Île-de-France, France