Biomedical subjects

Chela T James

Publications and source records attributed to Chela T James.

3 recordsLinked to original sources

PubMed2005

Retinoic acid down-regulates Tbx1 expression in vivo and in vitro.

Both Tbx1 and retinoic acid (RA) are key players in embryonic pharyngeal development; loss of Tbx1 produces DiGeorge syndrome-like phenotypes in mouse models as does disruption of retinoic acid homeostasis. We have demonstrated that perturbation of retinoic acid levels in the avian embryo produces altered Tbx1 expression. In vitamin A-deficient quails, which lack endogenous retinoic acid, Tbx1 expression patterns were disrupted early in development and expression was subsequently lost in all tissues. "Gain-of-function" experiments where RA-soaked beads were grafted into the pharyngeal region produced localized down-regulation of Tbx1 expression. In these embryos, analysis of Shh and Foxa2, upstream control factors for Tbx1, suggested that the effect of RA was independent of this regulatory pathway. Real-time polymerase chain reaction analysis of retinoic acid-treated P19 cells showed a dose-dependent repression of Tbx1 by retinoic acid. Repression of Tbx1 transcript levels was first evident after 8-12 hr in culture in the presence of retinoic acid, and to achieve the highest levels of repression, de novo protein synthesis was required.

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PubMed2002

Tooth development is independent of a Hox patterning programme.

Hox genes have a critical role in controlling the patterning processes of many tissues by imparting positional information in embryogenesis. Patterning of the pharyngeal component of the skull (the visceroskeleton) has been proposed to be influenced by this "Hox code." Recently, it has been shown that Hox genes are associated with the evolution of jaws, loss of Hox gene expression in the first branchial arch being necessary for the transition from the agnathan condition to the gnathostome condition. Teeth develop on the first branchial arch in mammals and, therefore, might be expected to be under the control of Hox genes in a manner similar to that of the cranial skeletal elements. However, we show that, unlike cartilage and bone, the development of teeth is not affected by alterations in Hoxa2 expression. Tooth development in the first arch was unaffected by overexpression of Hoxa2, whereas recombinations of second arch mesenchyme with first arch epithelium led to tooth development within a Hoxa2-positive environment. These data demonstrate that teeth develop from local interactions and that tooth formation is not under the axial patterning program specified by the Hox genes. We propose that the evolutionary development of teeth in the first branchial arch is independent of the loss of Hox expression necessary for the development of the jaw.

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PubMed2002

Misexpression of genes in mouse tooth germs using in vitro electroporation.

Mouse mandible primodia in vitro explant cultures are an excellent model for investigating tooth development. Mandibular arch epithelial-mesenchymal tissue recombinations and implantation of beads soaked in signaling proteins have revealed much about the early events of odontogenesis. These approaches do, however, suffer from several disadvantages, in particular the nonphysiological nature of beads soaked in very high concentrations of proteins and the inability to directly manipulate receptor and transcription factor gene expression. We have utilized the technique of DNA electroporation to deliver targeted gene expression to defined areas of mandibular arch epithelium or mesenchyme. This approach is being used to (a) ectopically express epithelial signals such as Shh and Bmp-4, (b) inhibit BMP and FGF signaling by expression of dominant negative receptors and antagonists, and (c) misexpress transcriptional factors in the mesenchyme. The technical aspects of electroporation are discussed, as well as preliminary findings.

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