Biomedical subjects

C M Griffith

Publications and source records attributed to C M Griffith.

22 records · Page 2Linked to original sources

PubMed1990

Effects of retinoic acid on the distribution of glycoconjugates during mouse tail bud development.

Retinoic acid (RA), a potent teratogen of caudal axial development in rodents, has been shown to alter glycoconjugates in a variety of embryonic tissues and teratocarcinomas. In this study, we examined its effects on the expression of cell surface and extracellular matrix glycoconjugates during tail bud development in mouse embryos by using lectin histochemistry. The lectins WGA, sWGA, and PNA showed striking differences in binding between RA-exposed and control embryos. Computer-assisted densitometry revealed a significant increase in binding of all three lectins to the extracellular material of the luminal and abluminal borders of the secondary neural tube and surrounding the notochord in RA-exposed embryos. RA-treated embryos also showed an increased binding affinity for the lectins sWGA and PNA to the cells of the notochord, while WGA showed increased binding to the neuroepithelial cells of the secondary neural tube. The results suggest that RA affects the expression of lectin binding sites during the early development of RA-induced caudal axial defects.

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PubMed1990

Sialoconjugates and development of the tail bud.

Using lectin histochemistry, we have previously shown that there are alterations in the distribution of glycoconjugates in the tail bud of chick embryos that parallel the developmental sequence of the caudal axis. If glycoconjugates or the cells bearing them play a role in caudal axial development, then, restriction of their availability by binding with lectins would be expected to produce abnormalities of caudal development. In the present study, we treated embryos at various stages of tail bud development by microinjection with a variety of lectins. Administration of WGA by sub-blastodermal injection resulted in high incidences of secondary neural tube and notochordal abnormalities in lectin-treated embryos. The incidence of malformations was dependent upon both the dose of WGA received and the stage of development at the time of treatment. Using an anti-WGA antibody, we have also shown binding of the lectin in regions where defects were found. The lectin WGA binds to the sialic acid residues of glycoconjugates and to N-acetylglucosamine. Treatment of embryos with Limulus polyphemus lectin (LPL), which also binds to sialic acid, produced results similar to those of WGA. Treatments using lectins with other sugar-binding specificities, including succinylated WGA (with N-acetylglucosamine specificity only) produced defects that differed from those produced by WGA and LPL, and only with the administration of much higher doses. The results suggest that glycoconjugates in general and sialoconjugates in particular, or the cells carrying them, may have a role in caudal axial development.

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PubMed1989

Direct effects of retinoic acid on the development of the tail bud in chick embryos.

Retinoic acid (RA) has been reported to induce vascular lesions and haematoma formation in the vicinity of the tail bud during the critical period for inducing abnormalities of tail bud development in hamsters (Wiley, '83; Tibbles and Wiley, '88), mice (Tibbles and Wiley, '88) and chicken embryos (Jelinek and Kistler, '81). Experiments were conducted to determine whether or not these vascular lesions were the primary cause of the malformations which they accompanied. Chick embryos were exposed for varying lengths of time to several dosages of RA. Primitive streaks or tail buds from treated embryos were then excised prior to vascularization and transplanted to the coelomic walls of untreated host embryos. The grafts were harvested at 3 or 6 days after grafting and processed for histological examination. Observations of serial sections of controls showed that the primitive streak and early (stage 13-14) tail bud were able to form neural tubes and a variety of other structures including ganglia, nerve fibres, and kidney tubules. Treatment of donor embryos with RA prior to grafting, however, affected the frequency and characteristics of the neural tubes and other tissues developing in the grafts. The effects of RA on development were correlated with both the dosage and length of exposure to the teratogen prior to grafting. Since the grafts were made before the appearance of blood vessels in the tail buds, we have concluded that the effects of RA on the development of tail bud tissues, and especially the secondary neural tube, are direct and are not mediated solely through the disruptive effects of vascular lesions seen in intact embryos.

Animals↗

PubMed1989

The distribution of cell surface glycoconjugates during mouse secondary neurulation.

During secondary neurulation in the mouse, the neural tube develops from the tail bud by caudal extension of the primary neurocoele. The mesenchymal cells of the tail bud become radially arranged around the neurocoele and undergo a mesenchymal to epithelial transformation to form a neuroepithelium. In order to study the expression of glycoconjugates during the morphogenesis of the secondary neural tube, 14 lectins were applied to serial sections of tail buds at various stages of development. In general, binding was fairly homogeneous during the early stages of tail bud development. However, as development progressed, several lectins became localized to specific structures. The changes were observed to parallel the ongoing development of the secondary neuraxis. sWGA, which is N-acetylglucosamine (GlcNAc) specific, bound mainly to the luminal surface of the secondary neurocoele and to a lesser extent, the notochord. WGA, which has both GlcNAc and sialic acid specificities, showed most intense binding at the luminal and abluminal surfaces of the secondary neurocoele. Binding by the lectin PNA was restricted to the extracellular matrix around the developing secondary neural tube. A comparison of the lectin binding patterns in mouse with those previously reported in chick, demonstrates a less elaborate pattern of lectin binding in murine embryos. This may suggest a less complex expression of glycoconjugates in rodents, in keeping with their comparatively simpler mechanism of secondary neurulation.

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