Cigarette smoking and anxiety disorders.
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Biomedical subjects
Publications and source records attributed to L Sarkar.
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Interactions between the Wnt (wingless) and hedgehog signaling pathways were first described as playing a role in establishing boundaries between ectodermal cells in Drosophila segmentation. During the initiation of mammalian tooth development, boundaries that distinguish oral from dental ectoderm must be formed to correctly position the sites of tooth formation. We describe a reciprocal relationship between the expression of Wnt-7b in presumptive oral ectoderm and Shh in presumptive dental ectoderm in mouse embryos that mark boundaries between these cells with different developmental fates. By using a murine retrovirus to ectopically express Wnt-7b in presumptive dental ectoderm in mandibular arch explants, we show that Shh expression in the ectoderm and Ptc expression in the underlying ectomesenchyme are down-regulated, and tooth development is subsequently arrested. This suggests that Wnt-7b acts to repress Shh expression in oral ectoderm, thus maintaining the boundaries between oral and dental ectodermal cells. Implantation of beads soaked in Shh protein into Wnt-7b-infected explants resulted in complete rescue of tooth development, confirming that the repressive action of Wnt-7b specifically affects Shh signaling.
Wnt extracellular signaling molecules have essential roles as regulators of cell proliferation, migration, differentiation, and in epithelial-mesenchymal interactions involved in tissue morphogenesis. Frizzled integral membrane proteins have been shown to function as receptors for Wnt signaling molecules. Vertebrates also produce secreted proteins related to Frizzled receptors, Frizzled-related proteins (FRPs), which contain the cysteine-rich domain of Frizzleds and appear to function as Wnt antagonists. Tooth development is regulated by a reciprocal series of epithelial-mesenchymal interactions, and many Wnt signaling pathway genes are expressed in the developing tooth at these sites. Here we report the expression of one FRP gene, Mfrzb1, in the rostral mesenchyme of the mandibular primordium. Using explant cultures, we show that expression of Mfrzb1 in the mandibular mesenchyme is under the control of signals derived from the overlying epithelium. Bead implantation experiments in vitro show that FGF8 induces Mfrzb1 expression, whereas BMP4 and SHH proteins have no effect. We studied the effect of ectopic MFrzb1 protein on the developing tooth germs by transplanting explants treated with Mfrzb1 protein into renal capsules, and found it to retard tooth development. This suggests that Wnt signaling is required early in tooth germ formation and that interference with signaling via addition of an antagonist results in retarded development and formation of smaller teeth.
We have carried out comparative in situ hybridisation analysis of six Wnt genes Wnts-3, -4, -5a, -6, -7b, and 10b together with Wnt receptor MFz6 and receptor agonist/antagonists MFrzb1 and Mfrp2 during murine odontogenesis from the earliest formation of the epithelial thickening to the early bell stage. Expression of Wnt-4, Wnt-6, and one Wnt receptor MFz6 was observed in the facial, oral and dental epithelium. Wnt10b was localised specifically to the presumptive dental epithelium. Wnts-3 and -7b were expressed in oral epithelium but showed no expression in the presumptive dental epithelium. Wnt-3 also showed no expression in the epithelial cells of the molar bud stage tooth germs, but showed restricted expression in the enamel knots which are signalling centres believed to be involved in regulating tooth shape. Wnts -6, -10b and MFz6 were also detected in the primary and secondary enamel knots. Wnt-5a and agonist/antagonists MFrzb1 and Mfrp2 were expressed in a graded proximo-distal (P-D) manner in mesenchymal cells during the early stages of tooth development with no overlying expression in the oral or dental epithelium. Wnt-5a and MFrzb1 show strong expression in the dental papilla mesenchyme.
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1. The growth of rats treated with 3,5-dimethyoxy salicylic acid was retarded in comparison to that of normal rats. 2. The free cholesterol level of plasma of rats treated with 3,5-dimethoxy salicylic acid diminished while the pyruvate level of erythrocyte under the same condition increased in comparison with their normal levels; but on administration of thiamine both the cholesterol and pyruvate levels became normal. 3. The growth of a thiamine dependent strain of S. aureus was retarded when the organism was incubated in the medium containing 3,5-dimethoxy salicylic acid and this growth can be restored with the supplementation of thiamine in the medium.
1. The antithiamine factor isolated from cotton seed (Bombex malabericum) was a light yellow amophous substance. 2. 1 mg of this antithiamine factor inactivated 20.5 mug of thiamine hydrochloride. 3. The antithiamine factor was characterized as 3,5-dimethoxy salicylic acid.