Anatomy and Embryology

, Volume 181, Issue 3, pp 195–213 | Cite as

Developmental cell death: morphological diversity and multiple mechanisms

  • Peter G. H. Clarke
Review Articles


Physiological cell death is a widespread phenomenon in the development of both vertebrates and invertebrates. This review concentrates on an aspect of developmental cell death that has tended to be neglected, the manner in which the cells are dismantled. It is emphasized that the dying cells may adopt one of at least three different morphological types: “apoptotic”, “autophagic”, and “non-lysosomal vesiculate”. These probably reflect a corresponding multiplicity of intracellular events. In particular, the destruction of the cytoplasm in these three types appears to be achieved primarily by heterophagy, by autophagy and by non-lysosomal degradation, respectively. The various mechanisms underlying both nuclear and cytoplasmic destruction are reviewed in detail. The multiplicity of destructive mechanisms needs to be born in mind in studies of other aspects of cell death such as the signals which trigger it, since different signals probably trigger different types of cell death.

Key words

Cell death Degeneration Embryo Development Ultrastructure 


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  1. Allison AC (1969) Lysosomes and cancer. In: Dingle JT, Fell HB (eds) Lysosomes in biology and pathology, vol 2. North-Holland Publishing Co, Amsterdam London, pp 178–204Google Scholar
  2. Andriès J-C (1975) Différenciation et mort cellulaires au cours de la métamorphose mésentérique de la larve d'Aeshna cyanea. J Microsc Biol Cell 24:327–350Google Scholar
  3. Andriès J-C (1977) Dégénérescence, phagocytose et rejet cellulaire au niveau du mésentéron d'Aeshna cyanea (Insecte, Odonate). Biol Cellulaire 29:203–208Google Scholar
  4. Ashford TP, Porter KR (1962) Cytoplasmic components in hepatic cell lysosomes. J Cell Biol 12:198–202Google Scholar
  5. Bataillon L (1891) Recherches anatomiques et expérimentales sur la métamorphose des amphibiens anoures. Ann de l'Univ Lyon 2:1–123Google Scholar
  6. Beaulaton J (1986) Programmed cell death. Cytochemical evidence for accumulation of calcium in mitochondria and its translocation into lysosomes: X-ray microanalysis in metamorphosing insect muscles. Histochem J 18:527–536Google Scholar
  7. Beaulaton J, Lockshin RA (1977) Ultrastructural study of the normal degeneration of the intersegmental muscles of Antheraea polyphemus and Manduca sexta (Insecta, Lepidoptera) with particular reference to cellular autophagy. J Morphol 154:39–58Google Scholar
  8. Beaulaton J, Lockshin RA (1982) The relation of programmed cell death to development and reproduction: Comparative studies and an attempt at classification. Int Rev Cytol 79:215–235Google Scholar
  9. Bellairs R (1961) Cell death in chick embryos as studied by electron microscopy. J Anat (Lond) 95:54–60Google Scholar
  10. Berg DK (1982) Cell death in neuronal development; regulation by trophic factors. Curr Top Neurobiol 6:297–331Google Scholar
  11. Bernelli-Zazzera A (1975) Ribosomes in dying liver cells. In: Keppler D (ed) Pathogenesis and mechanisms of liver cell necrosis. MTP Press, Lancaster, pp 103–111Google Scholar
  12. Bessis M (1964) Studies on cell agony and death: an attempt at classification. In: de Reuck AVS, Knight J (eds) Ciba Foundation Symposium on cellular injury. Churchill, London, pp 287–316Google Scholar
  13. Bishop GA, King JS (1982) Intracellular horseradish peroxidase injections for tracing neural connections. In: Mesulam M-M (ed) Tracing neural connections with horseradish peroxidase. IBRO Handbook Series. Wiley, Chichester, pp 185–247Google Scholar
  14. Blaser PF, Catsicas S, Clarke PGH (1988) Dependence of developing neurons on protein synthesis in their axonal terminal territory. Eur J Neurosci [Suppl] 1:83Google Scholar
  15. Boobis AR, Fawthrop DJ, Davies DS (1989) Mechanisms of cell death. Trends Pharmacol Sci 10:275–280Google Scholar
  16. Borgers M, Thoné F (1976) Further characterization of phosphatase activities using non-specific substrates. Histochem J 8:301–317Google Scholar
  17. Bowen ID (1981) Techniques for demonstrating cell death. In: Bowen ID, Lockshin RA (eds) Cell death in biology and pathology. Chapman & Hall, London, pp 379–444Google Scholar
  18. Bowen ID (1984) Laboratory techniques for demonstrating cell death. In: Davies I, Sigee DC (eds) Cell ageing and cell death. Soc Exp Biol Seminar Series Vol 25. Cambridge University Press, Cambridge, London, pp 5–40Google Scholar
  19. Bowen ID, Ryder TA (1974) Cell autolysis and deletion in the planarian Polycelis tenuis Iijima. Cell Tissue Res 154:265–274Google Scholar
  20. Bowen ID, Ryder TA (1976) Use of the p-nitrophenyl phosphate method for the demonstration of acid phosphatase during starvation and cell autolysis in the planarian Polycelis tenuis Iijima. Histochem J 8:319–329Google Scholar
  21. Bowen ID, Ryder TA, Dark C (1976) The effects of starvation on the planarian worm Polycelis tenuis. Cell Tissue Res 1:193–209Google Scholar
  22. Bowen ID, den Hollander JE, Lewis GHJ (1982) Cell death and acid phosphatase activity in the regenerating planarian Polycelis tenuis Iijima. Differentiation 21:160–167Google Scholar
  23. Brachet J, Decroly-Briers M, Hoyez J (1958) Contribution à l'étude des lysosomes au cours du développement embryonnaire. Bull Soc Chim Biol 40:2039–2048Google Scholar
  24. Brunk UT (1973) Lysosomes and residual bodies in neurons and in vitro cultivated glia cells. Acta Univ Upsaliensis 148:1–38Google Scholar
  25. Butterworth FM, LaTendresse BL (1973) Quantitative studies of cytochemical and cytological changes during cell death in the larval fat body of Drosophila melanogaster. J Insect Physiol 19:1487–1500Google Scholar
  26. Choi DW (1988) Glutamate neurotoxicity and diseases of the nervous system. Neuron 1:623–634PubMedGoogle Scholar
  27. Chu-Wang I-W, Oppenheim RW (1978) Cell death of motoneurons in the chick embryo spinal cord. I. A light and electron microscopic study of naturally-occurring and induced cell loss during development. J Comp Neurol 177:33–58Google Scholar
  28. Clarke J, Shannon LM (1976) The isolation and characterization of the glycopeptides from horseradish peroxidase isoenzyme C. Biochim Biophys Acta 427:428–442Google Scholar
  29. Clarke PGH (1982) Labelling of dying neurons by peroxidase injected intravascularly in chick embryos. Neurosci Lett 30:223–228Google Scholar
  30. Clarke PGH (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 16:955–969Google Scholar
  31. Clarke PGH (1985a) Neuronal death in the development of the vertebrate nervous system. Trends Neurosci 8:345–349CrossRefGoogle Scholar
  32. Clarke PGH (1985b) Neuronal death during development in the isthmo-optic nucleus of the chick: Sustaining role of afferents from the tectum. J Comp Neurol 234:365–379Google Scholar
  33. Clarke PGH, Egloff M (1988) Combined effects of deafferentation and de-efferentation on isthmo-optic neurons during the period of their naturally occurring cell death. Anat Embryol 179:103–108Google Scholar
  34. Clarke PGH, Hornung JP (1989) Changes in the nuclei of dying neurons as studied with thymidine autoradiography. J Comp Neurol 283:438–449Google Scholar
  35. Clarke PGH, Martin AH (1985) Effects of de-efferentation on chick spinal motoneurons: peroxidase uptake, and activities of acid phosphatase and N-acetyl-β-glucosaminidase. Cell Biol Int Rep 9:676Google Scholar
  36. Cohen JJ, Duke RC (1984) Glucocorticoid activation of a calcium-dependent endonuclease in thymocyte nuclei leads to cell death. J Immunol 132:38–42Google Scholar
  37. Collin R (1906–1907) Recherches cytologiques sur le développement de la cellule nerveuse. Nevraxe 8:181–309Google Scholar
  38. Cowan WM, Fawcett JW, O'Leary DDM, Stanfield BB (1984) Regressive events in neurogenesis. Science 225:1258–1265Google Scholar
  39. Creek KE, Sly WS (1984) The role of the phosphomannosyl receptor in the transport of acid hydrolases to lysosomes. In: Dingle JT, Dean RT, Sly W (eds) Lysosomes in biology and pathology, vol 7. Elsevier, Amsterdam New York Oxford, pp 63–82Google Scholar
  40. Cunningham TJ (1982) Naturally occurring neuron death and its regulation by developing neural pathways. Int Rev Cytol 74:163–186Google Scholar
  41. Decker RS (1974) Lysosomal packaging in differentiating and degenerating anuran lateral motor column neurons. J Cell Biol 61:599–612Google Scholar
  42. Decker RS (1976) Influence of thyroid hormones on neuronal death and differentiation in larval Rana pipiens. Dev Biol 49:101–118Google Scholar
  43. Decker RS (1978) Retrograde responses of developing lateral motor column neurons. J Comp Neurol 180:635–660Google Scholar
  44. De Duve C (1957) Les lysosomes: un nouveau groupe de granules cytoplasmiques. J Physiol (Paris) 49:113–115Google Scholar
  45. De Duve C (1958) Les lysosomes. Bull Acad R Méd Belgique, 6e série, 23:608–618Google Scholar
  46. De Duve C (1963) The lysosome concept. In: Reuck AVS, Camerson MP (eds) Lysosomes, J & A Churchill Ltd, London, pp 1–35Google Scholar
  47. De Duve C, Wattiaux R (1966) Functions of lysosomes. Annu Rev Physiol 28:435–492Google Scholar
  48. De Duve C, Pressman BC, Gianetto R, Wattiaux R, Appelmans F (1955) Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat-liver tissue. Biochem J 60:604–617Google Scholar
  49. Duprat AM (1969) Action de la cycloheximide sur des cellules embryonnaires d'amphibien en cours de différenciation — etude comparative avec les effects de la puromycine. Ann Embryol Morphol 2:179–190Google Scholar
  50. Duvall E, Wyllie AH, Morris RG (1985) Macrophage recognition of cells undergoing programmed cell death (apoptosis). Immunology 56:351–358Google Scholar
  51. Ericsson JLE (1969) Mechanism of cellular autophagy. In: Dingle JT, Fell HB (eds) Lysosomes in Biology and Pathology, vol 2. North Holland, Amsterdam, pp 345–394Google Scholar
  52. Farbman AI (1968) Electron microscopic study of palate fusion in mouse embryos. Dev Biol 18:93–116Google Scholar
  53. Finlay BL, Pallas SL (1989) Control of cell number in the developing mammalian visual system. Prog Neurobiol 32:207–234Google Scholar
  54. Flanagan AEH (1969) Differentiation and degeneration in the motor column of foetal mouse. J Morphol 129:281–305Google Scholar
  55. Fox GQ, Kirk C, Richardson GP (1988) An ultrastructural analysis of electromotor cell death in Torpedo marmorata and its counterpart in vitro. Cell Tissue Res 254:455–464Google Scholar
  56. Fox H (1970) Tissue degeneration: an electron microscopic study of the pronephros of Rana temporaria. J Embryol Exp Morphol 24:139–157Google Scholar
  57. Fox H (1972a) Tissue degeneration: an electron microscope study of the tail skin of Rana temporaria during metamorphosis. Arch Biol (Liège) 83:373–394Google Scholar
  58. Fox H (1972b) Sub-dermal and notochordal collagen degeneration in the tail of Rana temporaria: an electron microscopic study. Arch Biol (Liège) 83:395–405Google Scholar
  59. Fox H (1972c) Muscle degeneration in the tail of Rana temporaria larvae at metamorphic climax: an electron microscopic study. Arch Biol (Liège) 83:407–417Google Scholar
  60. Fox H (1973a) Degeneration of the tail notochord of Rana temporaria at metamorphic climax. Examination by electron microscopy. Z Zellforsch Mikrosk Anat 138:371–386Google Scholar
  61. 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 30:377–396Google Scholar
  62. Fox H (1974) The epidermis and its degeneration in the larval tail and adult body of Rana temporaria and Xenopus laevis (Amphibia: Anura). J Zool Lond 174:217–235Google Scholar
  63. Fox H (1975) Aspects of tail muscle ultrastructure and its degeneration in Rana temporaria. J Embryol Exp Morphol 34:191–207Google Scholar
  64. Fox H (1977a) The anuran tadpole skin: changes occurring in it during metamorphosis and some comparisons with that of the adult. In: Spearman RIC (ed) Comparative anatomy of the skin. Academic Press London, Symp Zool Soc Lond 39:269–289Google Scholar
  65. Fox H (1977b) A consideration of tail constituents in larvae of Rana temporaria: skin and muscle, an ultrastructural study. In: Raynaud AA (ed) Mécanismes de la rudimentation des organes chez les embryons de vertébrés. Colloq Int CNRS 266:93–112Google Scholar
  66. Giorgi F, Deri P (1976) Cell death in ovarian chambers of Drosophila melanogaster. J Embryol Exp Morphol 35:521–533Google Scholar
  67. Glaumann H, Ericsson JLE, Marzella L (1981) Mechanisms of intralysosomal degradation with special reference to autophagocytosis and heterophagocytosis of cell organelles. Int Rev Cytol 73:149–182Google Scholar
  68. Glücksmann A (1951) Cell deaths in normal vertebrate ontogeny. Biol Rev 26:59–86Google Scholar
  69. Goedert M, Otten U, Schäfer T, Schwab M, Thoenen H (1980) Immunosympathectomy: Lack of evidence for a complementmediated cytotoxic mechanism. Brain Res 201:399–409Google Scholar
  70. Groscurth P (1989) Cytotoxic effector cells of the immune system. Anat Embryol 180:109–119Google Scholar
  71. Hamburger V (1975) Cell death in the development of the lateral motor column of the chick embryo. J Comp Neurol 160:535–546Google Scholar
  72. Hamburger V, Oppenheim RW (1982) Naturally occurring neuronal death in vertebrates. Neurosci Comment 1:39–55Google Scholar
  73. Harmon B, Bell L, Williams L (1984) An ultrastructural study on the “meconium corpuscles” in rat foetal intestinal epithelium with particular reference to apoptosis. Anat Embryol 169:119–124Google Scholar
  74. Harrison JD, Borgers M, Thoné F (1979) Some observations on the phosphatase cytochemistry of the submandibular gland of cat. Histochem J 11:311–320Google Scholar
  75. Hickman S, Neufeld EF (1972) A hypothesis for I-cell disease: defective hydrolases that do not enter lysosomes. Biochem Biophys Res Commun 49:992–997Google Scholar
  76. Hinchliffe JR (1981) Cell death in embryogenesis. In: Bowen ID, Lockshin RA (eds) Cell death in biology and pathology. Chapman and Hall, London, pp 35–69Google Scholar
  77. Hinchliffe JR (1982) Cell death in vertebrate limb morphogenesis. In: Harrison RJ, Navaratnam V (eds) Progress in anatomy. Cambridge University Press, Cambridge, vol 2, pp 1–17Google Scholar
  78. Hinchliffe JR, Griffiths PJ (1984) Experimental analysis of the control of cell death in chick limb bud development. In: Davies I, Sigee DC (eds) Cell ageing and cell death. Soc Exp Biol Seminar Series Vol 25. Cambridge University Press, Cambridge, London, pp 223–242Google Scholar
  79. Hinrichsen CFL, Stevens GS (1974) Epithelial morphology during closure of the secondary palate in the rat. Arch Oral Biol 19:969–980Google Scholar
  80. Hoefsmit ECM, Eestermans IL, Korn C, Van Duijn P (1985) False localization of acid phosphatase activity in the nuclear envelope and endoplasmic reticulum of peritoneal macrophages. Histochem J 17:235–241Google Scholar
  81. Holtfreter J (1945) Neuralization and epidermization of gastrula ectoderm. J Exp Zool 98:161–209Google Scholar
  82. Holtzman E (1976) Lysosomes: A survey. Cell biology monographs, vol 3. Springer, Vienna New YorkGoogle Scholar
  83. Hornung JP, Koppel H, Clarke PGH (1989) Endocytosis and autophagy in dying neurons: An ultrastructural study in chick embryos. J Comp Neurol 283:425–437Google Scholar
  84. Hourdry J (1977a) Cytological and cytochemical changes in the intestinal epithelium during anuran metamorphosis. Int Rev Cytol Suppl 5:337–385Google Scholar
  85. Hourdry J (1977b) La dégénérescence de l'épithélium intestinal chez la larve d'anoure en métamorphose. Colloques CNRS 266, Paris, pp 125–136Google Scholar
  86. Hruban Z, Swift H, Wissler R (1962) Analog-induced inclusions in pancreatic acinar cells. J Ultrastruct Res 7:273–285Google Scholar
  87. Humbert W (1978) Intracellular and intramitochondrial binding of lanthanum in dark degenerating midgut cells of a collembolan (insect). Histochemistry 59:117–128Google Scholar
  88. Hume DA, Perry VH, Gordon S (1983) Immunohistochemical localization of macrophage-specific antigen in developing mouse retina: phagocytosis of dying neurons and differentiation of microglia cells to form a regular away in the plexiform layers. J Cell Biol 97:253–257Google Scholar
  89. Hurle JM (1988) Cell death in developing systems. Methods Achiev Exp Pathol 13:55–86Google Scholar
  90. Hurle J, Hinchliffe JR (1978) Cell death in the posterior necrotic zone (PNZ) of the chick wing-bud: a Stereoscan and ultrastructural survey of autolysis and cell fragmentation. J Embryol Exp Morphol 43:123–136Google Scholar
  91. Hurle JM, Lafarga M, Ojeda JL (1977) Cytological and cytochemical studies of the necrotic area of the bulbus of the chick embryo heart. J Embryol Exp Morphol 41:161–173Google Scholar
  92. Innocenti GM (1981) Transitory structures as substrate for developmental plasticity of the brain. Developments in Neuroscience, vol 13. Elsevier, North Holland, Amsterdam New York Oxford, pp 305–333Google Scholar
  93. Jimbow K, Szabo G, Fitzpatrick TB (1974) Ultrastructural investigation of autophagocytosis of melanosomes and programmed death of melanocytes in White Leghorn feathers: a study of morphogenetic events leading to hypomelanosis. Dev Biol 36:8–23Google Scholar
  94. Jones GW, Bowen ID (1979) The fine structural localization of acid phosphatase in pore cells of embryonic and newly hatched Deroceras reticulatum (Pulmonata: Stylommatophora. Cell Tissue Res 204:253–265Google Scholar
  95. Jones GW, Davis WL, Vinson SB (1982) A histochemical and X-ray microanalysis study of calcium changes in insect flight muscle degeneration in Solenopsis, the queen fire ant. J Histochem Cytochem 30:293–304Google Scholar
  96. Jurand A (1965) Ultrastructural aspects of early development of the forelimb buds in the chick and the mouse. Proc R Soc London Ser B 162:387–405Google Scholar
  97. Jurand A, Pavan C (1975) Ultrastructural aspects of histolytic processes in the salivary gland cells during metamorphic stages in Rhynchosciara hollaenderi (Diptera, Sciaridae). Cell Differ 4:219–236Google Scholar
  98. Kerr JFR (1965) A histochemical study of hypertrophy and ischaemic injury of rat liver with special reference to changes in lysosomes. J Pathol Bacteriol 90:419–455Google Scholar
  99. Kerr JFR (1971) Shrinkage necrosis: a distinct mode of cellular death. J Pathol 105:13–20PubMedGoogle Scholar
  100. Kerr JFR, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide ranging implications in tissue kinetics. Br J Cancer 26:239–257PubMedGoogle Scholar
  101. Kerr JFR, Harmon B, Searle J (1974) An electron-microscope study of cell deletion in the anuran tadpole tail during spontaneous metamorphosis with special reference to apoptosis of striated muscle fibres. J Cell Sci 14:571–585Google Scholar
  102. Kerr JFR, Searle J, Harmon BV, Bishop CJ (1987) Apoptosis. In: Potten CS (ed) Perspectives on mammalian cell death. Oxford University Press, Oxford, pp 93–128Google Scholar
  103. Kieny M, Sengel P (1974) La nécrose morphogène interdigitale chez l'embryon de poulet: effet de la cytochalasine B. Année Biol 13:57–68Google Scholar
  104. Koike T, Martin DP, Johnson EM Jr (1989) Role of Ca2+ channels in the ability of membrane depolarization to prevent neuronal death induced by trophic-factor deprivation: Evidence that levels of internal Ca2+ determine nerve growth factor dependence of sympathetic ganglion cells. Proc Natl Acad Sci USA 86:6421–6425Google Scholar
  105. Kömüves LG, Sass M, Kovács J (1985) Autophagocytosis in the larval midgut cells of Pieris brassicae during metamorphosis. Cell Tissue Res 240:215–221Google Scholar
  106. Koppel H, Lewis PD, Patel AJ (1983) Cell death in the external granular layer of normal and undernourished rats: further observations, including estimates of rate of cell loss. Cell Tissue Kinet 16:99–106Google Scholar
  107. Kovács J, Réz G (1979) Autophagocytosis. Acta Biol Hung 30:177–199Google Scholar
  108. Krstić R, Pexieder T (1972) Elektronenmikroskopische Darstellung des Zelluntergangs in den Herzbulbuswülsten des Hühnerembryos. Acta Anat (Basel) 82:470Google Scholar
  109. Krstić R, Pexieder T (1973) Ultrastructure of cell death in bulbar cushions of chick embryo heart. Z Anat Entwickl-Gesch 140:337–350Google Scholar
  110. Lamb AH (1984) Motoneuron death in the embryo. CRC Crit Rev Clin Neurobiol 1:141–179Google Scholar
  111. Lamborghini JE (1987) Disappearance of Rohon-Beard neurons from the spinal cord of larval Xenopus laevis. J Comp Neurol 264:47–55Google Scholar
  112. Levi-Montalcini R (1950) The origin and development of the visceral system in the spinal cord of the chick embryo. J Morphol 86:253–283Google Scholar
  113. Levi-Montalcini R, Aloe L (1981) Mechanism(s) of action of nerve growth factor in intact and lethally injured sympathetic nerve cells in neonatal rodents. In: Bowen ID, Lockshin RA (eds) Cell death in biology and pathology. Chapman & Hall, London, pp 295–327Google Scholar
  114. Levi-Montalcini R, Angeletti PU (1966) Immunosympathectomy. Pharmacol Rev 18:619–628Google Scholar
  115. Lockshin RA (1981) Cell death in metamorphosis. In: Bowen ID, Lockshin RA (eds) Cell death in biology and pathology. Chapman & Hall, London, pp 79–121Google Scholar
  116. Lockshin RA, Beaulaton J (1974) Programmed cell death. Life Sci 15:1549–1565Google Scholar
  117. Lockshin RA, Zakeri-Milovanovic Z (1984) Nucleic acids in cell death. In: Davies I, Sigee DC (eds) Cell ageing and cell death Cambridge University Press, Cambridge, pp 243–268Google Scholar
  118. Manasek FJ (1969) Myocardial cell death in the embryonic chick ventricle. J Embryol Exp Morphol 21:271–284Google Scholar
  119. Marovitz WF, Shugar JMA, Khan KM (1976) The role of cellular degeneration in the normal development of (rat) otocyst. Laryngoscope 86:1413–1425Google Scholar
  120. Martin DP, Schmidt RE, DiStefano PS, Lowry OH, Carter JG, Johnson EM Jr (1988) Inhibitors of protein synthesis and RNA synthesis prevent neuronal death caused by nerve growth factor deprivation. J Cell Biol 106:829–844Google Scholar
  121. Matsuura S, Morimoto T, Nagata S, Tashiro Y (1968) Studies on the posterior silk gland of the silkworm, Bombyx mori. II. Cytolytic processes in posterior silk gland cells during metamorphosis from larva to pupa. J Cell Biol 38:589–603Google Scholar
  122. Mego JL (1973) Protein digestion in isolated heterolysosomes. In: Dingle JT (ed) Lysosomes in biology and pathology, vol 3. North-Holland Publishing, Amsterdam, pp 138–168Google Scholar
  123. Michaels JE, Albright JT, Patt DI (1971) Fine structural observations on cell death in the epidermis of the external gills of the larval frog, Rana pipiens. Am J Anat 132:301–318Google Scholar
  124. Milaire J, Rooze M (1983) Hereditary and induced modifications of the normal necrotic patterns in the developing limb buds of the rat and mouse: facts and hypothesis. Arch Biol (Bruxelles) 94:459–490Google Scholar
  125. Monzon M, Yanes CM, Trujillo CM, Marrero A (1987) Cell death in the normal development of Gallotia galloti mesencephalon (Reptilia Lacertidae). An ultrastructural study. J Submicrosc Cytol 19:71–76Google Scholar
  126. Morris RG, Hangreaves AD, Duvall E, Wyllie AH (1984) Hormone-induced cell death. 2. Surface changes in thymocytes undergoing apoptosis. Am J Path 115:426–436Google Scholar
  127. Mottet NK, Hammar SP (1972) Ribosome crystals in necrotizing cells from the posterior necrotic zone of the developing chick limb. J Cell Sci 11:403–414Google Scholar
  128. Napolitano L (1963) Cytoplasmic bodies containing mitochondria, ribosomes, and rough surfaced endoplasmic reticulum in the small intestine of new born rats. J Cell Biol 18:478–481Google Scholar
  129. Navascués J, Martin-Partido G, Alvarez IS, Rodriguez-Gallardo L (1988) Cell death in suboptic necrotic centers of chick embryo diencephalon and their topographic relationship with the earliest optic fibre fascicles. J Comp Neurol 278:34–46Google Scholar
  130. Novikoff AB, Shin WY (1964) The endoplasmic reticulum in the Golgi zone and its relations to microbodies, Golgi apparatus, and autophagic vacuoles in rat liver cells. J Microsc 3:187–206Google Scholar
  131. Nussdorfer GG (1970) The fine structure of the newborn rat adrenal cortex II. Zona juxtamedullaris. Z Zellforsch 103:398–409Google Scholar
  132. O'Connor TM, Wyttenbach CR (1974) Cell death in the embryonic chick spinal cord. J Cell Biol 60:448–459Google Scholar
  133. Oppenheim RW (1981) Neuronal cell death and some related regressive phenomena during neurogenesis: a selective historical review and progress report. In: Cowan WM (ed) Studies in developmental neurobiology: essays in honor of Viktor Hamburger. Oxford University Press, New York, pp 74–133Google Scholar
  134. Oppenheim RW (1985) Naturally occurring cell death during neural development. Trends Neurosci 8:487–493Google Scholar
  135. Orrenius S, McConkey DJ, Bellomo G, Nicotera P (1989) Role of Ca2+ in toxic cell killing. Trends Pharmacol Sci 10:281–285Google Scholar
  136. Osinchak J (1966) Ultrastructural localization of some phosphatases in the prothoracic gland of the insect Leucophaea maderae. Z Zellforsch 72:236–248Google Scholar
  137. Pannese E (1976) An electron microscopic study of cell degeneration in chick embryo spinal ganglia. Neuropathol Appl Neurobiol 2:247–267Google Scholar
  138. Pannese E, Luciano L, Iurato S, Reale E (1976) Lysosomes in normal and degenerating neuroblasts of the chick embryo spinal ganglia. Acta Neuropathol (Berl) 36:209–220Google Scholar
  139. Pautou M, Kieny M (1971) Sur les mécanismes histologiques et cytologiques de la necrose morphogène interdigitale chez l'embryon de poulet. CR Acad Sci (Paris) Ser D 272:2025–2028Google Scholar
  140. Payen G (1972) Etude ultrastructurale de la dégénérescence cellulaire dans la glande androgène du Crabe Ocypode quadrata (Fabricius). Z Zellforsch 129:370–385Google Scholar
  141. Peluso JJ, England-Charlesworth C, Bolender DL, Steger RW (1980) Ultrastructural alterations associated with the initiation of follicular atresia. Cell Tissue Res 211:105–115Google Scholar
  142. Perry VH, Hume DA, Gordon S (1985) Immunohistochemical localization of macrophages and microglia in the adult and developing mouse brain. Neuroscience 15:313–326Google Scholar
  143. Pexieder T (1972) The tissue dynamics of heart morphogenesis. I. The cell death phenomena. A. Identification and morphology. Z Anat Entwickl-Gesch 137:270–284Google Scholar
  144. Philippe E, Garosi M, Droz B (1988) Influence of peripheral and central targets on subpopulations of sensory neurons expressing calbindin immunoreactivity in the dorsal root ganglion of the chick embryo. Neuroscience 26:225–232Google Scholar
  145. Pilar G, Landmesser L (1976) Ultrastructural differences during embryonic cell death in normal and peripherally deprived ciliary ganglia. J Cell Biol 68:339–356Google Scholar
  146. Pontremoli S, Melloni E, Horecker BL (1984) Limited proteolysis of cytosolic enzymes by lysosomal proteinases accessible to the cytosol. In: Dingle JT, Dean RT, Sly W (eds) Lysosomes in biology and pathology, vol 7. Elsevier, Amsterdam New York Oxford, pp 141–161Google Scholar
  147. Pratt RM, Greene RM (1976) Inhibition of palatal epithelial cell death by altered protein synthesis. Dev Biol 54:135–145Google Scholar
  148. Provis JM, Penfold PL (1988) Cell death and the elimination of retinal axons during development. Prog Neurobiol 31:331–347Google Scholar
  149. Rasch EM, Gawlik S (1964) Cytolysosomes in tissues of metamorphosing sciarid larvae. J Cell Biol 23:123AGoogle Scholar
  150. Sabatini MT, De Iraldi AP, De Robertis E (1965) Early effects of the antiserum (AS) of the nerve growth factor (NGF) on the structure of sympathetic neurons. J Exp Neurol 12:370–383Google Scholar
  151. Salzgeber B, Weber R (1966) Le régression du mésonéphros chez l'embryon de poulet. Etude des activités de la phosphatase acide et des cathepsines. Analyse biochimique, histochimique et observations au microscope électronique. J Embryol Exp Morphol 15:397–419Google Scholar
  152. Schanne FAX, Kane AB, Young EE, Farber JL (1979) Calcium dependence of toxic cell death: A final common pathway. Science 206:700–702Google Scholar
  153. Scharrer B (1966) Ultrastructural study of the regressing prothoracic glands of blattarian insects. Z Zellforsch 69:1–21Google Scholar
  154. Scheib D (1962) Les lysosomes et leurs roles dans quelques phénomènes biologiques. Année Biol 1:35–52Google Scholar
  155. Scheib D (1963) Properties and role of acid hydrolases of the Müllerian ducts during sexual differentiation in the male chick embryo. In: de Reuck AVS, Cameron MP (eds) Lysosomes. Ciba Foundation Symposium, Churchill, London, pp 264–277Google Scholar
  156. Scheib D (1965a) Structure fine du canal de Müller de l'embryon de Poulet: lésions cytoplasmiques du canal mâle en régression. CR Acad Sci (Paris) 260:1252–1254Google Scholar
  157. Scheib D (1965b) Sur la régression du canal de Müller mâle de l'embryon de poulet: localisation de la phosphatase acide au microscope électronique. CR Acad Sci (Paris) Ser D 261:5219–5221Google Scholar
  158. Scheib D (1977) Mécanismes cellulaires et déterminisme hormonal de la régression des canaux de Müller chez l'embryon de poulet: étude cytologique et biochemique. In: Mécanismes de la rudimentation des organes chez les embryons de vertébrés. Colloques CNRS 266, Paris, pp 59–70Google Scholar
  159. Scheib-Pfleger D, Wattiaux R (1962) Etude des hydrolases acides des canaux de Müller de l'embryon de poulet. Activités totales et solubles des canaux d'embryons de 8 à 10 jours d'incubation. Dev Biol 5:205–217Google Scholar
  160. Schin KS, Clever U (1965) Lysosomal and free acid phosphatase in salivary glands of Chironomus tentans. Science 150:1053–1055Google Scholar
  161. Schin KS, Clever U (1968) Ultrastructural and cytochemical studies of salivary gland regression in Chironomus tentans. Z Zellforsch 86:262–279Google Scholar
  162. Schweichel JU (1972) Das elektronenmikroskopische Bild des Abbaues der epithelialen Scheitelleiste während der Extremitätenentwicklung bei Rattenfeten. Z Anat Entwickl-Gesch 136:192–203Google Scholar
  163. Schweichel JU, Merker HJ (1973) The morphology of various types of cell death in prenatal tissues. Teratology 7:253–266Google Scholar
  164. Seinsch W, Schweichel JU (1974) Physiologic cell necrosis during the early development of muscles of the back in embryonic mice. Z Anat Entw Gesch 245:101–112Google Scholar
  165. Sengelaub DR, Jacobs LF, Finlay BL (1985) Regional differences in normally occurring cell death in the developing hamster lateral geniculate nuclei. Neurosci Lett 55:103–108Google Scholar
  166. Shepherd V, Schlesinger P, Stahl P (1983) Receptors for lysosomal enzymes and glycoproteins. Curr Top Membranes Trans 18:317–338Google Scholar
  167. Skudlarek MD, Novak EK, Swank RT (1984) Processing of lysosomal enzymes in macrophages and kidney. In: Dingle JT, Dean RT, Sly W (eds) Lysosomes in biology and pathology, vol 7. Elsevier, Amsterdam New York Oxford, pp 17–43Google Scholar
  168. Smiley GR, Dixon AD (1968) Fine structure of midline epithelium in developing palate of the mouse. Anat Rec 161:293–310Google Scholar
  169. Soberman RJ, Hoffstein S, Weissman G (1973) Direct evidence for suicide sac hypothesis of lysosomal enzyme release by monosodium urate. Arthritis Rheum 16:132–133Google Scholar
  170. Sohal GS, Weidman T (1978) Ultrastructural sequence of embryonic cell death in normal and peripherally deprived trochlear nucleus. Exp Neurol 61:53–64Google Scholar
  171. Stéphan-Dubois F, Lanot R, Bautz A-M (1974) Aspects structuraux des dégénérescences cellulaires aux cours des processus morphogénétiques. Année Biol 13:27–34Google Scholar
  172. Stocker RF, Edwards JS, Truman JW (1978) Fine structure of degenerating moth abdominal motor neurons after eclosion. Cell Tissue Res 191:317–331Google Scholar
  173. Sulston JE, Albertson DG, Thomson JN (1980) The Caenorhabditis elegans male: Postembryonic development of nongonadal structures. Dev Biol 78:542–576Google Scholar
  174. Thoenen H, Barde Y-A, Davies AM, Johnson JE (1987) Neurotrophic factors and neuronal death. In: Bock G, O'Connor M (eds) Selective neuronal death. Ciba Foundation Symposium 126. Wiley, Chichester, pp 82–95Google Scholar
  175. Truman JW (1987) The insect nervous system as a model system for the study of neuronal death. Curr Top Dev Biol 21:99–116Google Scholar
  176. Trump BF, Berezesky IK (1985) Cellular ion regulation and disease: A hypothesis. Curr Top Membranes Trans 25:279–319Google Scholar
  177. Trump BF, Mergner WJ (1974) Cell injury. In: Zweifach BW, Grant L, McCluskey RT (eds) The inflammatory process. Academic Press, New York, pp 115–257Google Scholar
  178. Ucker DS (1987) Cytotoxic T lymphocytes and glucocorticoids activate an endogenous suicide process in target cells. Nature 327:62–54Google Scholar
  179. Wahnschaffe U, Bartsch U, Fritzsch B (1987) Metamorphic changes within the lateral-line system of Anura. Anat Embryol 175:431–442Google Scholar
  180. Wyllie AH (1980) Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation. Nature 284:555–556PubMedGoogle Scholar
  181. Wyllie AH (1981) Cell death: a new classification separating apoptosis from necrosis. In: Bowen ID, Lockshin RA (eds) Cell death in biology and pathology. Chapman & Hall, New York, pp 9–34Google Scholar
  182. Wyllie AH, Morris RG (1982) Hormone-induced cell death. Purification and properties of thymocytes undergoing apoptosis after glucocorticoid treatment. Am J Pathol 109:78–87Google Scholar
  183. Wyllie AH, Kerr JFR, Currie AR (1973) Cell death in the normal neonatal rat adrenal cortex. J Pathol 111:255–261Google Scholar
  184. Wyllie AH, Duvall E, Blow JJ (1984a) Intracellular mechanisms in cell death in normal and pathological tissues. In: Davies I, Sigee DC (eds) Cell ageing and cell death. Cambridge University Press, Cambridge, pp 269–294Google Scholar
  185. Wyllie AH, Morris RG, Smith AL, Dunlop D (1984b) Chromatin cleavage in apoptosis: association with condensed chromatin morphology and dependence on macromolecular synthesis. J Pathol 142:67–78PubMedGoogle Scholar
  186. Yamada T, Ohyama H, Kinjo Y, Watanabe M (1981) Evidence for the internucleosomal breakage of chromatin in rat thymocytes irradiated in vitro. Radiat Res 85:544–553Google Scholar
  187. Young RW (1984) Cell death during differentiation of the retina in the mouse. J Comp Neurol 229:362–373Google Scholar
  188. Zhivotovsky BD, Zvonareva NB, Hanson KP (1981) Characteristics of rat thymus chromatin degradation products after whole body X-irradiation. Int J Radiat Biol 39:437–440Google Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • Peter G. H. Clarke
    • 1
  1. 1.Institut d'AnatomieLausanneSwitzerland

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