Programmed cell death (PCD) is a widespread phenomenon in the development of vertebrates. In most cases, dying cells during development exhibit generalized morphological features typical of apoptosis. We analyzed the morphological features of dying cells in the developing axial structures of 5 human embryos between 5 and 8 weeks of postovulatory age. Cell death in the axial structures, i.e. spinal cord, notochord and surrounding mesenchyme and somites, was analyzed using light and electron microscopy. Tissue samples were taken from the cervicothoracic region of normal human conceptuses. Two morphological types of cell death were found: apoptosis which was characterized by round or semilunar nuclear chromatin condensations, condensation and shrinkage of the cytoplasm and formation of apoptotic bodies, and cell death without the morphological features of apoptosis which was characterized by pyknotic nuclear chromatin condensations, vacuolated cytoplasm and the formation of numerous intercellular spaces. Apoptotic death occurred during the 5th week of normal development in all the axial structures. Later, apoptotic death appeared in all the axial structures, with the exception of the notochord, where some dying cells displayed features of secondary necrosis. According to our findings, apoptosis seems to be the most frequently observed type of PCD, but it is not the exclusive type of morphological cell death during the development of axial structures in human embryos.

Keywords:
Apoptosis, Cell death, programmed, Axial organs, Development, Embryo, human
1.
Alles, A.J., K.K. Sulik (1990) Retinoic acid-induced spina bifida, evidence for a pathological mechanism. Development 108: 73–81.
2.
Barde, Y.A. (1989) Trophic factors and neuronal survival. Neuron 2: 1525–1534.
3.
Clarke, P.G.H. (1984) Identical populations of phagocytes and dying neurons revealed by intravascularly injected horseradish peroxidase, and by endogenous glutaraldehyde-resistant acid phosphatase in the brains of chick embryos. Histochem J 16: 955–969.
4.
Clarke, P.G.H. (1990) Developmental cell death: Morphological diversity and multiple mechanisms. Anat Embryol 181: 195–213.
5.
Chu-Wang, I.W., R.W. Oppenheim (1978) Cell death of motoneurons in the chick embryo spinal cord. A light and electron microscopic study of naturally occurring and induced cell loss during development. J Comp Neurol 177: 33–57.
6.
Decker, R.S. (1974) Lysosomal packaging in differentiating and degenerating anuran lateral motor column neurons. J Cell Biol 61: 599–612.
7.
Fallon, J.F., B.K. Simandl (1978) Evidence of a role of cell death in the disappearance of the embryonic human tail. Am J Anat 152: 111–130.
8.
Fox, H. (1973a) Degeneration of the tail notochord of Rana temporaria at metamorphic climax. Examination by electron microscopy. Zellforsch Mikrosk Anat 138: 371–386.
9.
Fox, H. (1973b) Degeneration of the nerve cord in the tail of Rana temporaria during metamorphic climax: A study by electron microscopy. J Embryol Exp Morphol 30: 377–396.
10.
Galić, M., M. Saraga-Babić, A. Švajger (1986) Electron microscopic observations on the notochord of human embryos and fetuses. Proc JASA 424: 239–273.
11.
Graham, A., P. Francis West, P. Brickell, A. Lumsden (1994) The signaling molecule BMP4 mediates apoptosis in rhombencephalic neural crest. Nature 372: 684–686.
12.
Gruneberg, H. (1963) The Pathology of Development. A Study of Inherited Skeletal Disorders in Animals. Oxford, Blackwell.
13.
Homma, S., H. Yaginuma, R.W. Oppenheim (1994) Programmed cell death during the earliest stages of spinal cord development in the chick embryo, a possible means of early phenotypic selection. J Comp Neurol 238: 425–437.
14.
Jacobson, M.D., M. Weil, M.C. Raff (1997) Programmed cell death in animal development. Cell 88: 347–354.
15.
Kerr, J.F., B. Harmon, J. Searle (1974) An electron-microscope study of cell deletion in the anuran tadpole tail during spontaneous metamorphosis with special reference to apoptosis of striated muscle fibers. J Cell Sci 14: 571–585.
16.
Kerr, J.F., J. Searle, B.V. Harmon, C.J. Bishop (1987) Apoptosis; in Potten, C.S. (ed): Prospectives on Mammalian Cell Death. Oxford, Oxford University Press, pp 93–128.
17.
Kerr, J.F., A.H. Wyllie, A.R. Currie (1972) Apoptosis: A basic biological phenomenon with wide-raging implication in tissue kinetics. Br J Cancer 26: 239–257.
18.
Koseki, C., D. Herzlinger, Q. Al-Awquati (1992) Apoptosis in metanephric development. J Cell Biol 119: 1327–1333.
19.
Lehtonen, E., V. Stefanović, M. Saraga-Babić (1995) Changes in the expression of intermediate filaments and desmoplakins during development of human notochord. Differentiation 59: 43–49.
20.
Levi-Montalcini, R. (1987) The nerve growth factor 35 years later. Science 237: 1154–1162.
21.
Majno, G., I. Joris (1995) Apoptosis, oncosis and necrosis. Am J Pathol 146: 3–15.
22.
Milligan, C.E., D. Prevette, H. Yaginuma, S. Homma, C. Cardwell, L.C. Fritz, K.J. Tomaselli, R.W. Oppenheim, L.M. Schwartz (1995) Peptide inhibitors of the ICE protease family arrest programmed cell death in motoneurons in vivo and in vitro. Neuron 15: 385–393.
23.
Monzon, Y., C.M. Yanes, C.M. Trujillo, A. Marrero (1987) Cell death in the normal development of Gallotia galloti mesencephalon (Reptilia Lacertidae): An ultrastructural study. J Submicrosc Cytol 19: 71–76.
24.
Nijhawan, D., N. Honarpour, X. Wang (2000) Apoptosis in neural development and disease. Annu Rev Neurosci 23:73–87.
25.
O’Connor, T.M., C.R. Wyttenbach (1974) Cell death in the embryonic chick spinal cord. J Cell Biol 60: 448–459.
26.
Oppenheim, R.W. (1991) Cell death during development of the nervous system. Annu Rev Neurosci 14:453–501.
27.
O’Rahilly, R., F. Müller (1987) Developmental stages in human embryos. Carnegie Inst Wash 637: 246.
28.
Placzek, M., M. Tessier-Lavigne, T. Yamanda, T. Jessel, J. Dodd (1990) Mesodermal control of neural cell identity: Floor plate induction by the notochord. Science 250: 985–988.
29.
Raff, M.C. (1992) Social controls of cell survival and cell death. Nature 356: 397–400.
30.
Sanders, E.J., M.K. Khare, V.C. Ooi, R. Bellairs (1986) An experimental and morphological analysis of the tail bud mesenchyme in the chick embryo. Anat Embryol 174: 179–185.
31.
Sanders, E.J., M.A. Wride (1995) Programmed cell death in development. Int Rev Cytol 163: 105–173.
32.
Saraga-Babić, M. (1991) Development of the notochord in normal and malformed human embryos and fetuses. Int J Dev Biol 35: 345–352.
33.
Saraga-Babić, M., E. Lehtonen, A. Švajger, J. Wartiovaara (1994) Morphological and immunohistochemical characteristics of axial structures in the transitory human tail. Ann Anat 176: 277–286.
34.
Saraga-Babić, M., V. Stefanović, J. Wartiovaara, E. Lehtonen (1993) Spinal cord-notochord relationship in normal human embryos and in a human embryo with double spinal cord. Acta Neuropathol 86: 509–514.
35.
Saraga-Babić M., A. Švajger, M. Galić (1984) Light and electron microscopic investigation on developmental changes in the human notochord. Rad Med Fak Zagreb 25: 111–120.
36.
Schoenwolf, G.C. (1981) Ultrastructural observations on cell necrosis during formation of the neural tube in mouse embryos. Anat Embryol 162: 183–197.
37.
Schweichel, J.U., H.J. Merker (1973) The morphology of various types of cell deaths in prenatal tissues. Teratology 7: 253–266.
38.
Smith, J.L., G.C. Schoenwolf (1989) Notochordal induction of cell wedging in the chick neural plate and its role in neural tube formation. J Exp Zool 250: 49–62.
39.
Steller, H. (1995) Mechanisms and genes of cellular suicide. Science 267: 1445–1449.
40.
Straaten, H.W.M. van, J. Drukker (1987) Influence of the notochord on the morphogenesis of the neural tube. NATO ASI Series; in Wolf, J.R., J. Sievers, M. Berry (eds): Mesenchymal-Epithelial Interactions in Neural Development. Berlin, Springer, vol H5, pp 153–162.
41.
Trout, J.J., J.A. Buckwalter, K.C. Moore, S.K. Landas (1982) Ultrastructure of the human intervertebral disc. II. Cells of the nucleus pulposus. Anat Rec 204: 307–314.
42.
Wyllie, A.H. (1981) Cell death: A new classification separating apoptosis from necrosis; in Bowen, I.D., R.A. Lockshin (eds): Cell Death in Biology and Pathology. New York, Chapman & Hall, pp 9–33.
43.
Wyllie, A.H. (1992) Apoptosis and the regulation of cell numbers in normal and neoplastic tissues: An overview. Cancer Metastasis Rev 11: 95–103.
© 2001 S. Karger AG, Basel
2001
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.