Abstract
Among the basic cellular events that shape the developing brain, programmed cell death (also called apoptosis) plays an essential role (Cowan et al. 1984; Oppenheim 1991). Although cell death during the development of the vertebrate nervous system was first described by anatomists of the nineteenth century, a mechanistic understanding of these events started only in the latter half of this century through two lines of research. First, the identification of nerve growth factor (NGF) by R. Levi-Montalcini and colleagues showed that cells died if deprived of trophic molecules and thus established the foundation for the “trophic theory” of neural development. Second, H. R. Horvitz pioneered genetic studies of programmed cell death in the nematode Caenorhabditis elegans and elucidated a genetic pathway involved in this process. Because the targeted disruption of specific genes in the mouse can now be performed, we can test directly whether the same cell death machinery is conserved in mammals. Moreover, the similarity of the organization and development of the central nervous system between the mouse and higher primates makes it an ideal experimental system for understanding the roles of programmed cell death in normal human brain development and congenital malformations. The present chapter focuses on the recent gene targeting studies elucidating the evolutionarily conserved cell death machinery in the context of mouse brain development.
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References
Adams JM, Cory S (1998) The Bd-2 protein family: arbiters of cell survival. Science 281: 13221326
Cecconi F, Alvarez-Bolado G, Meyer BI, Roth KA, Gruss P (1998) Apafl (CED-4 homolog) regulates programmed cell death in mammalian development. Cell 94: 727–737
Chinnaiyan AM, O’Rourke K, Lane BR, Dixit VM (1997) Interaction of CED-4 with CED-3 and CED-9: a molecular framework for cell death. Science 275: 1122–1126
Conradt B, Horvitz HR (1998) The C. elegans protein EGL-1 is required for programmed cell death and interacts with the Bcl-2-like protein CED-9. Cell 93: 519–529
Cowan WM, Fawcett JW, O’Leary DD, Stanfield BB (1984) Regressive events in neurogenesis. Science 225: 1258–1265
Deckwerth TL, Elliott JL, Knudson CM, Johnson EM Jr, Snider WD, Korsmeyer SJ (1996) BAX is required for neuronal death after trophic factor deprivation and during development. Neuron 17: 401–411
Dong C, Yang DD, Wysk M, Whitmarsh AJ, Davis RJ, Flavell RA (1998) Defective T cell differentiation in the absence of Jnkl. Science 282: 2092–2095
Eksioglu YZ, Scheffer IE, Cardness P, Knoll J, Dimario F, Ramsby G, Berg M, Kamuro K, Berkovic SF, Duyk M, Parisi J, Huttenlocher PR, Walsh CA (1996) Periventricular heterotopia: an X-linked dominant epilepsy locus causing aberrant cerebral cortical development. Neuron 16: 77–87
Ellis RE, Horvitz HR (1991) Two C. elegans genes control the programmed deaths of specific cells in the pharynx. Development 112: 591–603
Glucksmann A (1951) Cell deaths in normal vertebrate ontogeny. Biol Rev 26: 59–86
Gupta S, Barrett T, Whitmarsh AJ, Cavanagh J, Sluss HK, Derijard B, Davis RJ (1996) Selective
interaction of JNK protein kinase isoforms with transcription factors. EMBO J 15: 2760–2770 Hakem R, Hakem A, Duncan GS, Henderson JT, Woo M, Soengas MS, Elia A, de la Pompa JL
Kagi D, Khoo W, Potter J, Yoshida R, Kaufman SA, Lowe SW, Penninger JM, Mak TW (1998) Differential requirement for caspase 9 in apoptotic pathways in vivo. Cell 94: 339–352
Hamburger V (1992) History of the discovery of neuronal death in embryos. J Neurobiol23: 1116–1123
Hamburger V (1934) The effects of wing bud extirpation on the development of the central nervous system in chick embryos. J Exp Zool 68: 449–494
Hamburger V (1939) Motor and sensory hyperplasia following limb-bud transplantations in chick embryos. Physiol Zool 12: 258–84
Hengartner MO, Horvitz HR (1992) C. elegans cell survival gene ced-9 encodes a functional homolog of the mammalian proto-oncogene bd-2. Cell 76: 665–676
Hengartner MO, Ellis RE, Horvitz HR (1992) Caenorhabditis elegans gene ced-9 protects cells from programmed cell death. Nature 356: 494–499
Hockenbery D, Nunez G, Milliman C, Schreiber RD, Korsmeyer SJ (1990) Bd-2 is an inner
mitochondrial membrane protein that blocks programmed cell death. Nature 348: 334–336 Ip YT, Davis RJ (1998) Signal transduction by the c-Jun N-terminal kinase (JNK)-from
inflammation to development. Curr Opin Cell Biol 10:205–219
Kallen B (1955) Cell degeneration during normal ontogenesis of the rabbit brain. J Anat 89: 153–161
Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide ranging implications in tissue kinetics. Br J Cancer 26: 239–257
Kluck RM, Bossy-Wetzel E, Green DR, Newmeyer DD (1997) The release of cytochrome c from mitochondria: a primary site for Bd-2 regulation of apoptosis. Science 275: 1132–36
Kuan CY, Yang DD, Samanta Roy DR, Davis RJ, Rakic P, Flavell RA (1999) The Jnkl and Jnk2 protein kinases are required for regional specific apoptosis during early brain development. Neuron 22: 667–676
Kuida K, Zheng TS, Na S, Kuan CY, Yang D, Karasuyama H, Rakic P, Flavell RA (1996) Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice. Nature 384: 368–372
Kuida K, Haydar TF, Kuan CY, Gu Y, Taya C, Karasuyama H, Su MSS, Rakic P, Flavell RA (1998) Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9. Cell 94: 325–337
Lee KS, Schottler F, Collins JL, Lanzino G, Couture D, Rao A, Hiramatsu KI, Goto Y, Hong SC, Caber H, Yamamoto H, Chen ZF, Bertram E, Berr S, Omary R, Scrable H, Jackson T, Goble J, Eisenman L (1997) A genetic animal model of human neocortical heterotopia associated with seizures. J Neurosci 17: 6236–6242
Levi-Montalcini R (1987) The nerve growth factor 35 years later. Science 237: 1154–1162
Li P, Nijhawan D, Buduhardjo I, Srinivasula SM, Ahmad M, Almemri ES, Wang X (1997)
Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91:479–489
Liu X, Kim CN, Yang J, Jemmerson R, Wang X (1996) Induction of apoptotic program in cell-extracts: requirement for dATP and cytochrome c. Cell 86: 147–157
Martin JH, Mohit AA, Miller CA (1996) Developmental expression in the mouse nervous system of the p493F12 SAP kinase. Brain Res Mol Brain Res 35: 47–57
Martinou JC, Dubois-Dauphin M, Staple JK, Rodriguez I, Frankowski H, Missotten M, Albertini
Talabot D, Catsicas S, Pietra C, Huarte J (1994) Overexpression of BCL-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia. Neuron 13: 1017–1030
Merry DE, Korsmeyer SJ (1997) Bd-2 gene family in the nervous system. Annu Rev Neurosci 20: 245–267
Metzstein MM, Hengartner MO, Tsung N, Ellis RE, Horvitz HR (1996) Transcriptional regulator of programmed cell death encoded by Caenorhabditis elegans gene ces-2. Nature 382: 545–547
Metzstein MM, Stanfield GM, Horvitz HR (1998) Genetics of programmed cell death in C. elegans: past, present and future. Trends Genet 14: 410–416
Motoyama N, Wang F, Roth KA, Sawa H, Nakayama KI, Nakayama K, Negishi I, Senju S, Zhang
Fuiji S, Loh DY (1995) Massive cell death of immature hematopoietic cells and neurons in Bcl-x-deficient mice. Science 267: 1506–1510
Oltvai ZO, Milliman CL, Korsemeyer SJ (1993) Bd-2 heterodimerize in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74: 609–19
Oppenheim RW (1991) Cell death during development of the nervous system. Annu Rev Neurosci 14: 453–501
Pan G, O’Rouke K, Dixit VM (1998) Caspase-9, Bcl-xL, and Apaf-1 form a ternary complex. J Biol Chem 273: 5841–5845
Rakic P (1988) Specification of cerebral cortical areas. Science 241: 170–176
Shindler KS, Latham CB, Roth KA (1997) Bax deficiency prevents the increased cell death of immature neurons in bcl-x-deficient mice. J Neurosci 17: 3112–3119
Spector MS, Desnoyers S, Hoeppner DJ, Hengartner MO (1997) Interaction between the C. elegans cell-death regulators CED-9 and ED-4. Nature 385: 653–656
Thomaidou D, Mione MC, Cavanagh JF, Parnavelas JG (1997) Apoptosis and its relation to the cell cycle in the developing cerebral cortex. J Neurosci 17: 1075–1085
Thornberry NA, Lazebnik Y (1998) Caspases: enemies within. Science 281: 1312–1316
Vaux DL, Weissman IL, Kim SK (1992) Prevention of programmed cell death in Caenorhabditis elegans by human bd-2. Science 258: 1955–1957
Veis DJ, Sorenson CM, Shutter JR, Korsmeyer SJ (1993) Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair. Cell 75: 229–240
White FA, Keller-Peck CR, Knudson CM, Korsemeyer SJ, Snider WD (1998) Widespread elimination of naturally occurring neuronal death in Bax-deficient mice. J Neurosci 18: 1428–1439
Xue D, Shaham S, Horvitz HR (1996) The Caenorhabditis elegans cell-death protein CED-3 is a cysteine protease with substrate specificities similar to those of the human CPP32 protease. Genes Dev 10: 1073–1083
Yang DD, Kuan CY, Whitmarsh AJ, Rincón M, Zheng TS, Davis RJ, Rakic P, Flavell RA (1997) Absence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the Jnk3 gene. Nature 389: 865–870
Yang J, Liu X, Bhalla K, Kim N, Ibrado AM, Cai J, Peng TI, Jones DP, Wang X (1997) Prevention of apoptosis by Bd-2: Release of cytochrome c from mitochondria blocked. Science 275: 1129–1132
Yang DD, Conze D, Whitmarsh AJ, Barrett T, Davis RJ, Rincón M, Flavell RA (1998) Differ- entiation of CD4+ T cells to Thl cells requires MAP kinase JNK2. Immunity 9: 575–585
Yoshida H, Kong Y, Yoshida R, Elia AJ, Hakem A, Hakem R, Penninger JM, Mak TW (1998) Apafl is required for mitochondrial pathways of apoptosis and brain development. Cell 94: 739–750
Yuan J, Shaham S, Ledoux S, Ellis HM, Horvitz HR (1993) The C. elegans cell death gene ced-3 encodes a protein similar to the mammalian interleukin-1 beta-converting enzyme. Cell 75: 641–652
Zou H, Henzel WJ, Liu X, Lutschg A, Wang X (1997) Apaf-1, a human protein homologous to C. elegans CED-4, participates in cytochrome c-dependent activation of caspase-3. Cell 90: 405–413
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Kuan, CY., Flavell, R.A., Rakic, P. (2000). Programmed Cell Death in Mouse Brain Development. In: Goffinet, A.M., Rakic, P. (eds) Mouse Brain Development. Results and Problems in Cell Differentiation, vol 30. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-48002-0_6
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DOI: https://doi.org/10.1007/978-3-540-48002-0_6
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