Summary
Mouse embryos explanted at various stages during neurulation were cultured for 20–28 h in the presence of 25–900 μg/ml of 5-bromodeoxyuridine (BUdR). BUdR strongly inhibited closure of the cranial neural tube, which was found to be stage-dependent. When mouse embryos were exposed to BUdR after development of the concave curvature in the neuroepithelium of the midbrain to the upper hindbrain regions, they became insensitive to the drug-induced open cranial neural tube. Histological observations showed that BUdR interfered with interkinetic migration and cytokinesis of the neuroepithelial cells. These cellular abnormalities were not dependent on the morphological development of the cranial neural folds. The3H-BUdR experiment confirmed that the label was mostly incorporated into the DNA fraction.
Similar content being viewed by others
References
Abbott, J., and Holtzer, H., The loss of phenotypic traits by differentiated cells. V. The effect of 5-bromodeoxyuridine on cloned chondrocytes. Proc. natl Acad. Sci. USA59 (1968) 1144–1151.
Bannigan, J., and Langman, J., The cellular effect of 5-bromode-oxyuridine on the mammalian embryo. J. Embryol. exp. Morph.50 (1979) 123–135.
Buckley, S. K. L., Steele, C. E., and New, D. A. T., In vitro development of early postimplantation rat embryos. Devl Biol.65 (1978) 396–403.
Burnside, B., Microtubules and microfilaments in newt neurulation. Devl Biol.26 (1971) 416–441.
Coleman, J. R., Coleman, A. W., and Hartline, E. J. H., A clonal study of the reversible inhibition of muscle differentiation by the halogenated thymidine analog 5-bromodeoxyuridine. Devl Biol.19 (1969) 527–548.
Fujita, S., Kinetics of cellular proliferation. Exp. Cell Res.28 (1962) 52–60.
Garner, W., The effect of 5-bromodeoxyuridine on early mouse embryos in vitro. J. Embryol. exp. Morph.32 (1974) 849–855.
Geelen, J. A. G., and Langman, J., Closure of the neural tube in the cephalic region of the mouse embryo. Anat. Rec.189 (1977) 625–640.
Golbus, M. S., and Epstein, C. J., Effect of 5-bromodeoxyuridine on pre-implantation mouse embryo development. Differentiation2 (1974) 143–149.
Gontcharoff, M., and Mazia, D., Developmental consequences of introduction of bromouracil into the DNA of sea urchin embryos during early division stages. Exp. Cell Res.46 (1967) 315–327.
Goz, B., The effects of incorporation of 5-halogenated deoxyuridines into the DNA of eukaryotic cells. Pharmac. Rev.29 (1978) 249–272.
Huxley, H. E., Muscular contraction and cell motility. Nature243 (1973) 445–449.
Karfunkel, P., The activity of microtubules and microfilaments in neurulation in the chick. J. exp. Zool.181 (1972) 289–302.
Kaufman, M., Cephalic neurulation and optic vesicle formation in the early mouse embryo. Am. J. Anat.155 (1979) 425–444.
Lee, H., Deshpande, A. K., and Kalmus, G. W., The effects of 5-bromodeoxyuridine (BUrd) on morphogenesis of the early chick embryo. Wilhelm Roux Arch.174 (1974) 102–106.
Lee, H., Deshpande, A. K., and Kalmus, G. W., Studies on effects of 5-bromodeoxyuridine on the development of explanted early chick embryos. J. Embryol. exp. Morph.32 (1974) 835–848.
Lee, H., Hikida, R. S., and Levin, M. A., Neural-tube defects caused by 5-bromodeoxyuridine in chicks. Teratology14 (1976) 89–98.
Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J., Protein measurement with the folin phenol reagent. J. biol. Chem.193 (1951) 265–275.
Lyser, K. M., Early differentiation of motor neuroblasts in the chick embryo as studied by electron microscopy. 1. General aspects. Devl Biol.10 (1964) 433–466.
Messier, P-E., and Auclair, C., Effect of cytochalasin B on interkinetic nuclear migration in the chick embryo. Devl Biol.36 (1974) 218–223.
Miura, Y., and Wilt, F. H., The effects of 5-bromodeoxyuridine on yolk sac erythropoiesis in the chick embryo. J. Cell Biol.48 (1971) 523–532.
Miwa, I., Okuda, J., Maeda, K., and Okuda, G., Mutarotase effect on colorimetric determination of blood glucose with β-D-glucose oxidase. Clinica chim. Acta37 (1972) 538–540.
Morriss, G. M., and New, D. A. T., Effect of oxygen concentration on morphogenesis of cranial neural folds and neural crest in cultured rat embryos. J. Embryol. exp. Morph.54 (1979) 17–35.
Morriss, G. M., Growth and development of pattern in the cranial neural epithelium of rat embryos during neurulation. J. Embryol. exp. Morph.65 (1981) 225–241.
Murphy, M. L., Dose-response relationships in growth-inhibiting drugs in the rat: time of treatment as a teratological determinant, in: Teratology: Principles and Techniques, pp. 161–184. Eds J. G. Wilson and J. Warkany. Univ. of Chicago Press, Chicago 1965.
Nakashima, K., and Fujiki, Y., Effects of 5-bromodeoxyuridine on in vitro development of mouse embryos in the early somitic stage. Experientia39 (1983) 202–203.
New, D. A. T., Coppola, P. T., and Terry, S., Culture of explanted rat embryos in rotating tubes. J. Reprod. Fert.35 (1973) 135–138.
Pollard, D. R., Baran, M. M., and Bachvarova, R., The effect of 5-bromodeoxyuridine on cell division and differentiation of preimplantation mouse embryos. J. Embryol. exp. Morph.35 (1976) 169–178.
Pollard, T. D., and Weihing, R. R., Actin and myosin and cell movement. CRC Crit. Rev. Biochem.2 (1974) 1–65.
Ruddick, J. A., and Runner, M. N., 5-FU in chick embryos as a source of label for DNA and a depressant of protein synthesis. Teratology10 (1974) 39–46.
Ruffolo, P. R., and Ferm, V. H., The embryocidal and teratogenic effects of 5-bromodeoxyuridine in the pregnant hamster. Lab. Invest.14 (1965) 1547–1553.
Schroeder, T. E., Preliminary notes. Cytokinesis: Filaments in the cleavage fullow. Exp. Cell Res.53 (1968) 272–276.
Schroeder, T. E., The contractile ring. II. Determining its brief existence, volumetric changes, and vital role in cleaving Arbacia eggs. J. Cell Biol.53 (1972) 419–434.
Scott, W. J., Pathogenesis of bromodeoxyuridine-induced polydactyly. Teratology23 (1981) 383–389.
Shah, R. M., and Mackay, R. A., Teratological evaluation of 5-fluorouracil and 5-bromo-2-deoxyuridine on hamster fetuses. J. Embryol. exp. Morph.43 (1978) 47–54.
Sherman, M. I., and Atienza, S. B., Effects of bromodeoxyuridine, cytosine arabinoside and colcemid upon in vitro development of mouse blastocysts. J. Embryol. exp. Morph.34 (1975) 467–484.
Skalko, R. G., Packard, D. S., Schwendimann, R. N., and Raggio, J. F., The teratogenic response of mouse embryos to 5-bromodeoxyuridine. Teratology4 (1971) 87–94.
Spindle, A. I., Inhibition of early postimplantation development of cultured mouse embryos by bromodeoxyuridine. J. exp. Zool.202 (1977) 17–26.
Steele, C. E., and New, D. A. T., Serum variants causing the formation of double hearts and other abnormalities in explanted rat embryos. J. Embryol. exp. Morph.31 (1974) 707–719.
Tencer, R., and Brachet, J., Studies on the effects of 5-bromode-oxyuridine (BUdR) on differentiation. Differentiation1 (1973) 51–64.
Waterman, R. E., Topographical changes along the neural fold associated with neurulation in the hamster and mouse. Am. J. Anat.146 (1976) 151–172.
Webster, W., and Langman, J., The effect of cytochalasin B on the neuroepithelial cells of the mouse embryo. Am. J. Anat.152 (1978) 209–222.
Wise, L. D., and Scott, W. J., Incorporation of 5-bromo-2′-deoxyuridine into mesenchymal limb-bud cells destined to die: relationship to polydactyly induction in rats. J. Embryol. exp. Morph.72 (1982) 125–141.
Author information
Authors and Affiliations
Additional information
Acknowledgment. This work was supported by Grant-in-Aids for scientific research No. 557469 and 58480391 from the Ministry of Education, Japan.
Rights and permissions
About this article
Cite this article
Nakashima, K., Ninomiya, H. & Fujiki, Y. The effect of 5-bromodeoxyuridine on mouse embryos during neurulation in vitro. Experientia 40, 924–929 (1984). https://doi.org/10.1007/BF01946441
Issue Date:
DOI: https://doi.org/10.1007/BF01946441