Skip to main content

Advertisement

SpringerLink
Log in

Ontogenic cell death in the nigrostriatal system

  • Review
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Like most neural systems, dopamine neurons of the substantia nigra undergo apoptotic natural cell death during development. In rodents, this occurs largely postnatally and is biphasic with an initial major peak just after birth and a second minor peak on postnatal day 14. As envisioned by classic neurotrophic theory, this event is regulated by interactions with the target of these neurons, the striatum, because a developmental target lesion results in an augmented natural cell death event with fewer nigral dopamine neurons surviving into adulthood. Until recently, the striatal target-derived neurotrophic factors providing developmental support of dopamine neurons were unknown, but there is now growing evidence that glial-cell-line-derived neurotrophic factor (GDNF) serves as a physiologic limiting neurotrophic factor for these neurons during the first phase of natural cell death. During this phase, intrastriatal injection of GDNF diminishes the natural cell death event and neutralizing antibodies augment it. Sustained overexpression of GDNF in the striatum throughout development in a unique double transgenic mouse model results in an increased number of dopamine neurons surviving the first phase of natural cell death. However, this increase does not persist into adulthood. Therefore, other factors or mechanisms must play important roles in the determination of the mature number of nigral dopamine neurons. Further elucidation of these mechanisms will be important in the development of neuroprotective and cell replacement therapies for Parkinson’s disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1A, B
Fig. 2A, B
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Akerud P, Alberch J, Eketjall S, Wagner J, Arenas E (1999) Differential effects of glial cell line-derived neurotrophic factor and neurturin on developing and adult substantia nigra dopaminergic neurons. J Neurochem 73:70–78

    Article  CAS  PubMed  Google Scholar 

  • Alexi T, Hefti F (1993) Trophic actions of transforming growth factor α on mesencephalic dopaminergic neurons developing in culture. Neuroscience 55:903–918

    Article  CAS  PubMed  Google Scholar 

  • Alonso-Vanegas MA, Fawcett JP, Causing CG, Miller FD, Sadikot AF (1999) Characterization of dopaminergic midbrain neurons in a DBH:BDNF transgenic mouse. J Comp Neurol 413:449–462

    Article  CAS  PubMed  Google Scholar 

  • Altar CA, DiStefano PS (1998) Neurotrophin trafficking by anterograde transport. Trends Neurosci 21:433–437

    Article  CAS  PubMed  Google Scholar 

  • Altar CA, Boylan CB, Fritsche M, Jones BE, Jackson C, Wiegand SJ, Lindsay RM, Hyman C (1994) Efficacy of brain-derived neurotrophic factor and neurotrophin-3 on neurochemical and behavioral deficits associated with partial nigrostriatal dopamine lesions. J Neurochem 63:1021–1032

    CAS  PubMed  Google Scholar 

  • Barde YA (1989) Trophic factors and neuronal survival. Neuron 2:1525–1534

    Article  CAS  PubMed  Google Scholar 

  • Barde YA, Edgar D, Thoenen H (1982) Purification of a new neurotrophic factor from mammalian brain. EMBO J 1:549–553

    CAS  PubMed  Google Scholar 

  • Beck KD, Irwin I, Valverde J, Brennan T, Langston JW, Hefti F (1996) GDNF induces a dystonia-like state in neonatal rats and stimulates dopamine and serotonin synthesis. Neuron 16:665–673

    Article  CAS  PubMed  Google Scholar 

  • Blum M (1998) A null mutation in TGF-alpha leads to a reduction in midbrain dopaminergic neurons in the substantia nigra. Nat Neurosci 1:374–377

    Article  CAS  PubMed  Google Scholar 

  • Blum M, Weickert CS (1995) GDNF mRNA expression in normal postnatal development, aging, and in weaver mutant mice. Neurobiol Aging 16:925–929

    Article  CAS  PubMed  Google Scholar 

  • Burke RE, Macaya A, DeVivo D, Kenyon N, Janec EM (1992) Neonatal hypoxic-ischemic or excitotoxic striatal injury results in a decreased adult number of substantia nigra neurons. Neuroscience 50:559–569

    Article  CAS  PubMed  Google Scholar 

  • Burke RE, Antonelli M, Sulzer D (1998) Glial cell line-derived neurotrophic growth factor inhibits apoptotic death of postnatal substantia nigra dopamine neurons in primary culture. J Neurochem 71:517–525

    CAS  PubMed  Google Scholar 

  • Cacalano G, Farinas I, Wang LC, Hagler K, Forgie A, Moore M, Armanini M, Phillips H, Ryan AM, Reichardt LF, Hynes M, Davies A, Rosenthal A (1998) GFRalpha1 is an essential receptor component for GDNF in the developing nervous system and kidney. Neuron 21:53–62

    Article  CAS  PubMed  Google Scholar 

  • Cho J, Kholodilov NG, Burke RE (2003) The developmental time course of glial cell line-derived neurotrophic factor (GDNF) and GDNF receptor alpha-1 mRNA expression in the striatum and substantia nigra. Ann NY Acad Sci 991:284–287

    CAS  Google Scholar 

  • Cho J, Kholodilov NG, Burke RE (2004) Patterns of developmental mRNA expression of neurturin and GFRalpha2 in the rat striatum and substantia nigra do not suggest a role in the regulation of natural cell death in dopamine neurons. Brain Res Dev Brain Res 148:143–149

    Article  CAS  PubMed  Google Scholar 

  • Choi-Lundberg DL, Bohn MC (1995) Ontogeny and distribution of glial cell line-derived neurotrophic factor (GDNF) mRNA in rat. Dev Brain Res 85:80–88

    Article  CAS  Google Scholar 

  • Chun HS, Yoo MS, DeGiorgio LA, Volpe BT, Peng D, Baker H, Peng C, Son JH (2002) Marked dopaminergic cell loss subsequent to developmental, intranigral expression of glial cell line-derived neurotrophic factor. Exp Neurol 173:235–244

    Article  CAS  PubMed  Google Scholar 

  • Clarke PGH (1985) Neuronal death in the development of the vertebrate nervous system. Trends Neurosci 8:345–349

    Article  Google Scholar 

  • Clarke PGH (1990) Developmental cell death: morphological diversity and multiple mechanisms. Anat Embryol 181:195–213

    CAS  PubMed  Google Scholar 

  • Clarke PGH, Oppenheim RW (1995) Neuron death in vertebrate development: in vivo methods. In: Schwartz LM, Osborne BA (eds) Methods in cell biology: cell death. Academic, New York, pp 277–321

  • Coyle JT (1977) Biochemical aspects of neurotransmission in the developing brain. Int Rev Neurobiol 20:65–102

    CAS  PubMed  Google Scholar 

  • Coyle JT, Schwarcz R (1976) Lesion of striatal neurones with kainic acid provides a model for Huntington’s chorea. Nature 263:244–246

    CAS  PubMed  Google Scholar 

  • El-Khodor BF, Burke RE (2002) Medial forebrain bundle axotomy during development induces apoptosis in dopamine neurons of the substantia nigra and activation of caspases in their degenerating axons. J Comp Neurol 452:65–79

    Article  PubMed  Google Scholar 

  • Enomoto H, Araki T, Jackman A, Heuckeroth RO, Snider WD, Johnson EMJ, Milbrandt J (1998) GFR alpha1-deficient mice have deficits in the enteric nervous system and kidneys. Neuron 21:317–324

    Article  CAS  PubMed  Google Scholar 

  • Freeman RS, Estus S, Johnson EM (1994) Analysis of cell cycle related gene expression in postmitotic neurons selective induction of cyclin D1 during programmed cell death. Neuron 12:343–355

    Article  CAS  PubMed  Google Scholar 

  • Gallyas F, Wolff JR, Bottcher H, Zaborsky L (1980) A reliable and sensitive method to localize terminal degeneration and lysosomes in the central nervous system. Stain Tech 55:299–306

    CAS  Google Scholar 

  • Ganguly A, Oo TF, Rzhetskaya M, Pratt R, Yarygina O, Momoi T, Kholodilov N, Burke RE (2004) CEP11004, a novel inhibitor of the mixed lineage kinases, suppresses apoptotic death in dopamine neurons of the substantia nigra induced by 6-hydroxydopamine. J Neurochem 88:469–480

    CAS  PubMed  Google Scholar 

  • Golden JP, DeMaro JA, Osborne PA, Milbrandt J, Johnson EMJ (1999) Expression of neurturin, GDNF, and GDNF family-receptor mRNA in the developing and mature mouse. Exp Neurol 158:504–528

    Article  CAS  PubMed  Google Scholar 

  • Groc L, Bezin L, Jiang H, Jackson TS, Levine RA (2001) Bax, Bcl-2, and cyclin expression and apoptosis in rat substantia nigra during development. Neurosci Lett 306:198–202

    Article  CAS  PubMed  Google Scholar 

  • Groc L, Jackson HT, Jiang H, Bezin L, Koubi D, Corcoran GB, Levine RA (2002) Nitric oxide synthase inhibition during development: effect on apoptotic death of dopamine neurons. Brain Res Dev Brain Res 138:147–153

    Article  CAS  PubMed  Google Scholar 

  • Hattori T, McGeer PL (1973) Synaptogenesis in the corpus striatum of infant rat. Exp Neurol 38:70–79

    Article  CAS  PubMed  Google Scholar 

  • Hemmendinger LM, Garber BB, Hoffmann PC, Heller A (1981) Target neuron-specific process formation by embryonic mesencephalic dopamine neurons in vitro. Proc Natl Acad Sci USA 78:1264–1268

    CAS  PubMed  Google Scholar 

  • Herrup K, Sunter K (1987) Numerical matching during cerebellar development: quantitative analysis of granule cell death in staggerer mouse chimeras. J Neurosci 7:829–836

    CAS  PubMed  Google Scholar 

  • Hoffmann PC, Hemmendinger LM, Kotake C, Heller A (1983) Enhanced dopamine cell survival in reaggregates containing target cells. Brain Res 274:275–281

    Article  CAS  PubMed  Google Scholar 

  • Horger BA, Nishimura MC, Armanini MP, Wang LC, Poulsen KT, Rosenblad C, Kirik D, Moffat B, Simmons L, Johnson EJ, Milbrandt J, Rosenthal A, Björklund A, Vandlen RA, Hynes MA, Phillips HS (1998) Neurturin exerts potent actions on survival and function of midbrain dopaminergic neurons. J Neurosci 18:4929–4937

    CAS  PubMed  Google Scholar 

  • Hyman C, Hofer M, Barde YA, Juhasz M, Yancopoulos GD, Squinto SP, Lindsay RM (1991) BDNF is a neurotrophic factor for dopaminergic neurons of the substantia nigra. Nature 350:230–232

    Article  CAS  PubMed  Google Scholar 

  • Jackson-Lewis V, Vila M, Djaldetti R, Guegan C, Liberatore G, Liu J, O’Malley KL, Burke RE, Przedborski S (2000) Developmental cell death in dopaminergic neurons of the substantia nigra of mice. J Comp Neurol 424:476–488

    Article  CAS  PubMed  Google Scholar 

  • Janec E, Burke RE (1993) Naturally occurring cell death during postnatal development of the substantia nigra of the rat. Mol Cell Neurosci 4:30–35

    Article  Google Scholar 

  • Jeon BS, Kholodilov NG, Oo TF, Kim S, Tomaselli KJ, Srinivasan A, Stefanis L, Burke RE (1999) Activation of caspase-3 in developmental models of programmed cell death in neurons of the substantia nigra. J Neurochem 73:322–333

    Article  CAS  PubMed  Google Scholar 

  • Kalsbeek A, Voorn P, Buijs RM (1992) Development of dopamine-containing systems in the CNS. In: Björklund A, Hokfelt T, Tohyama M (eds) Handbook of chemical neuroanatomy, vol 10. Ontogeny of transmitters and peptides in the CNS. Elsevier, Amsterdam, pp 63–112

  • Kelly WJ, Burke RE (1996) Apoptotic neuron death in rat substantia nigra induced by striatal excitotoxic injury is developmentally dependent. Neurosci Lett 220:85–88

    Article  CAS  PubMed  Google Scholar 

  • Kholodilov N, Yarygina O, Oo TF, Zhang H, Sulzer D, Dauer WT, Burke RE (2004) Regulation of the development of mesencephalic dopaminergic systems by the selective expression of glial cell line-derived neurotrophic factor in their targets. J Neurosci 24:3136–3146

    Article  CAS  PubMed  Google Scholar 

  • Kluck RM, Bossy-Wetzel E, Green DR, Newmeyer DD (1997) The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science 275:1132–1136

    Article  CAS  PubMed  Google Scholar 

  • Knusel B, Beck KD, Winslow JW, Rosenthal A, Burton LE, Widmer HR, Nikolics K, Hefti F (1992) Brain-derived neurotrophic factor administration protects basal forebrain cholinergic but not nigral dopaminergic neurons from degenerative changes after axotomy in the adult rat brain. J Neurosci 12:4391–4402

    CAS  PubMed  Google Scholar 

  • Kotzbauer PT, Lampe PA, Heuckeroth RO, Golden JP, Creedon DJ, Johnson EMJ, Milbrandt J (1996) Neurturin, a relative of glial-cell-line-derived neurotrophic factor. Nature 384:467–470

    Article  CAS  PubMed  Google Scholar 

  • Krammer EB (1980) Anterograde and transsynaptic degeneration “en cascade” in basal ganglia induced by intrastriatal injection of kainic acid: an animal analogue of Huntington’s disease. Brain Res 196:209–221

    Article  CAS  PubMed  Google Scholar 

  • Lapchak PA, Beck KD, Araujo DM, Irwin I, Langston JW, Hefti F (1993) Chronic intranigral administration of brain-derived neurotrophic factor produces striatal dopaminergic hypofunction in unlesioned adult rats and fails to attenuate the decline of striatal dopaminergic function following medial forebrain bundle transection. Neuroscience 53:639–650

    Article  CAS  PubMed  Google Scholar 

  • Lauder JM, Bloom FE (1975) Ontogeny of monoamine neurons in the locus coeruleus, raphe nuclei and substantia nigra of the rat. J Comp Neurol 163:251–264

    CAS  PubMed  Google Scholar 

  • Lazar LM, Blum M (1992) Regional distribution and developmental expression of epidermal growth factor and transforming growth factor-alpha mRNA in mouse brain by a quantitative nuclease protection assay. J Neurosci 12:1688–1697

    CAS  PubMed  Google Scholar 

  • Ledda F, Paratcha G, Ibanez CF (2002) Target-derived GFRalpha1 as an attractive guidance signal for developing sensory and sympathetic axons via activation of Cdk5. Neuron 36:387–401

    Article  CAS  PubMed  Google Scholar 

  • Leibrock J, Lottspeich F, Hohn A, Hofer M, Hengerer B, Masiakowski P, Thoenen H, Barde YA (1989) Molecular cloning and expression of brain-derived neurotrophic factor. Nature 341:149–152

    Article  CAS  PubMed  Google Scholar 

  • Lin L-FH, Doherty DH, Lile JD, Bektesh S, Collins F (1993) GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons. Science 260:1130–1132

    CAS  PubMed  Google Scholar 

  • Linden R (1994) The survival of developing neurons: a review of afferent control. Neuroscience 58:671–682

    Article  CAS  PubMed  Google Scholar 

  • Lindsay RM (1993) Brain-derived neurotrophic factor: an NGF-related neurotrophin. In: Loughlin SE, Fallon JH (eds) Neurotrophic factors. Academic Press, San Diego, pp 257–284

  • Lopez-Martin E, Caruncho HJ, Rodriguez-Pallares J, Guerra MJ, Labandeira-Garcia JL (1999) Striatal dopaminergic afferents concentrate in GDNF-positive patches during development and in developing intrastriatal striatal grafts. J Comp Neurol 406:199–206

    Article  CAS  PubMed  Google Scholar 

  • Lundberg C, Wictorin K, Björklund A (1994) Retrograde degenerative changes in the substantia nigra pars compacta following an excitotoxic lesion of the striatum. Brain Res 644:205–212

    Article  CAS  PubMed  Google Scholar 

  • Macaya A, Munell F, Gubits RM, Burke RE (1994) Apoptosis in substantia nigra following developmental striatal excitotoxic injury. Proc Natl Acad Sci USA 91:8117–8121

    CAS  PubMed  Google Scholar 

  • Maisonpierre PC, Belluscio L, Friedman B, Alderson RF, Wiegand SJ, Furth ME, Lindsay RM, Yancopoulos GD (1990) NT-3, BDNF, and NGF in the developing rat nervous system: parallel as well as reciprocal patterns of expression. Neuron 5:501–509

    Article  CAS  PubMed  Google Scholar 

  • Marchand R, Poirer LJ (1983) Isthmic origin of neurons of the rat substantia nigra. Neuroscience 9:373–381

    Article  CAS  PubMed  Google Scholar 

  • Marti MJ, James CJ, Oo TF, Kelly WJ, Burke RE (1997) Early developmental destruction of terminals in the striatal target induces apoptosis in dopamine neurons of the substantia nigra. J Neurosci 17:2030–2039

    CAS  PubMed  Google Scholar 

  • Mayford M, Bach ME, Huang YY, Wang L, Hawkins RD, Kandel ER (1996) Control of memory formation through regulated expression of a CaMKII transgene. Science 274:1678–1683

    Article  CAS  PubMed  Google Scholar 

  • Mehmet H (2000) Caspases find a new place to hide. Nature 403:29–30

    Article  CAS  PubMed  Google Scholar 

  • Oiwa Y, Yoshimura R, Nakai K, Itakura T (2002) Dopaminergic neuroprotection and regeneration by neurturin assessed by using behavioral, biochemical and histochemical measurements in a model of progressive Parkinson’s disease. Brain Res 947:271–283

    Article  CAS  PubMed  Google Scholar 

  • Oo TF, Burke RE (1997) The time course of developmental cell death in phenotypically defined dopaminergic neurons of the substantia nigra. Dev Brain Res 98:191–196

    Article  CAS  Google Scholar 

  • Oo TF, Blazeski R, Harrison SMW, Henchcliffe C, Mason CA, Roffler-Tarlov S, Burke RE (1996) Neuron death in the substantia nigra of weaver mouse occurs late in development and is not apoptotic. J Neurosci 16:6134–6145

    CAS  PubMed  Google Scholar 

  • Oo TF, Siman R, Burke RE (2002) Distinct nuclear and cytoplasmic localization of caspase cleavage products in two models of induced apoptotic death in dopamine neurons of the substantia nigra. Exp Neurol 175:1–9

    Article  CAS  PubMed  Google Scholar 

  • Oo TF, Kholodilov N, Burke RE (2003) Regulation of natural cell death in dopaminergic neurons of the substantia nigra by striatal GDNF in vivo. J Neurosci 23:5141–5148

    CAS  PubMed  Google Scholar 

  • Oppenheim RW (1991) Cell death during development of the nervous system. Ann Rev Neurosci 14:453–501

    Article  CAS  PubMed  Google Scholar 

  • Paratcha G, Ledda F, Baars L, Coulpier M, Besset V, Anders J, Scott R, Ibanez CF (2001) Released GFRalpha1 potentiates downstream signaling, neuronal survival, and differentiation via a novel mechanism of recruitment of c-Ret to lipid rafts. Neuron 29:171–184

    Article  CAS  PubMed  Google Scholar 

  • Pasinetti GM, Morgan DG, Finch CE (1991) Disappearance of GAD-mRNA and tyrosine hydroxylase in substantia nigra following striatal ibotenic acid lesions: evidence for transneuronal regression. Exp Neurol 112:131–139

    Article  CAS  PubMed  Google Scholar 

  • Pichel JG, Shen L, Sheng HZ, Granholm A-C, Drago J, Grinberg A, Lee EJ, Huang SP, Saarma M, Hoffer BJ, Sariola H, Westphal H (1996) Defects in enteric innervation and kidney development in mice lacking GDNF. Nature 382:73–76

    Article  CAS  PubMed  Google Scholar 

  • Prochiantz A, Porzio U di, Kato A, Berger B, Glowinski J (1979) In vitro maturation of mesencephalic dopaminergic neurons from mouse embryos is enhanced in presence of their striatal target cells. Proc Natl Acad Sci USA 76:5387–5391

    CAS  PubMed  Google Scholar 

  • Purves D, Lichtman JW (1985) Principles of neural development. Sinauer, Sunderland

  • Raoul C, Henderson CE, Pettmann B (1999) Programmed cell death of embryonic motoneurons triggered through the Fas death receptor. J Cell Biol 147:1049–1062

    Article  CAS  PubMed  Google Scholar 

  • Raoul C, Estevez AG, Nishimune H, Cleveland DW, deLapeyriere O, Henderson CE, Haase G, Pettmann B (2002) Motoneuron death triggered by a specific pathway downstream of Fas. Potentiation by ALS-linked SOD1 mutations. Neuron 35:1067–1083

    Article  CAS  PubMed  Google Scholar 

  • Rayport S, Sulzer D, Shi WX, Sawasdikosol S, Monaco J, Batson D, Rajendran G (1992) Identified postnatal mesolimbic dopamine neurons in culture morphology and electrophysiology. J Neurosci 12:4264–4280

    CAS  PubMed  Google Scholar 

  • Saji M, Reis DJ (1987) Delayed transneuronal death of substantia nigra neurons prevented by gamma-aminobutyric acid agonist. Science 235:66–68

    CAS  PubMed  Google Scholar 

  • Sanchez MP, Silos-Santiago I, Frisen J, He B, Lira SA, Barbacid M (1996) Renal agenesis and the absence of enteric neurons in mice lacking GDNF. Nature 382:70–73

    Article  CAS  PubMed  Google Scholar 

  • Schaar DG, Sieber BA, Dreyfus CF, Black IB (1993) Regional and cell specific expression of GDNF in rat brain. Exp Neurol 124:368–371

    Article  CAS  PubMed  Google Scholar 

  • Scorrano L, Korsmeyer SJ (2003) Mechanisms of cytochrome c release by proapoptotic BCL-2 family members. Biochem Biophys Res Commun 304:437–444

    Article  CAS  PubMed  Google Scholar 

  • Stefanis L, Burke RE (1996) Transneuronal degeneration in substantia nigra pars reticulata following striatal excitotoxic injury in adult rat: time course, distribution, and morphology of cell death. Neuroscience 74:997–1008

    CAS  PubMed  Google Scholar 

  • Stromberg I, Björklund L, Johansson M, Tomac A, Collins F, Olson L, Hoffer B, Humpel C (1993) Glial cell line derived neurotrophic factor is expressed in the developing but not adult striatum and stimulates developing dopamine neurons in vivo. Exp Neurol 124:401–412

    Article  CAS  PubMed  Google Scholar 

  • Tepper JM, Damlama M, Trent F (1994) Postnatal changes in the distribution and morphology of rat substantia nigra dopaminergic neurons. Neuroscience 60:469–477

    Article  CAS  PubMed  Google Scholar 

  • Tomac A, Widenfalk J, Lin LH, Kohno T, Ebendal T, Hoffer BJ, Olson L (1995) Retrograde axonal transport of glial cell line-derived neurotrophic factor in the adult nigrostriatal system suggests a trophic role in the adult. Proc Natl Acad Sci USA 92:8274–8278

    CAS  PubMed  Google Scholar 

  • Tomozawa Y, Appel SH (1986) Soluble striatal extracts enhance development of mesencephalic dopaminergic neurons in vitro. Brain Res 399:111–124

    Article  CAS  PubMed  Google Scholar 

  • Treanor JJ, Goodman L, Sauvage F de, Stone DM, Poulsen KT, Beck CD, Gray C, Armanini MP, Pollock RA, Hefti F, Phillips HS, Goddard A, Moore MW, Buj-Bello A, Davies AM, Asai N, Takahashi M, Vandlen R, Henderson CE, Rosenthal A (1996) Characterization of a multicomponent receptor for GDNF. Nature 382:80–83

    Article  CAS  PubMed  Google Scholar 

  • Vila M, Jackson-Lewis V, Vukosavic S, Djaldetti R, Liberatore G, Offen D, Korsmeyer SJ, Przedborski S (2001) Bax ablation prevents dopaminergic neurodegeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. Proc Natl Acad Sci USA 98:2837–2842

    Article  CAS  PubMed  Google Scholar 

  • Wetts R, Herrup K (1983) Direct correlation between Purkinje and granule cell number in the cerebella of lurcher chimeras and wild-type mice. Dev Brain Res 10:41–47

    Article  Google Scholar 

  • Widenfalk J, Nosrat C, Tomac A, Westphal H, Hoffer B, Olson L (1997) Neurturin and glial cell line-derived neurotrophic factor receptor-beta (GDNFR-beta), novel proteins related to GDNF and GDNFR-alpha with specific cellular patterns of expression suggesting roles in the developing and adult nervous system and in peripheral organs. J Neurosci 17:8506–8519

    CAS  PubMed  Google Scholar 

  • Wilcox JN, Derynck R (1988) Localization of cells synthesizing transforming growth factor-alpha mRNA in the mouse brain. J Neurosci 8:1901–1904

    CAS  PubMed  Google Scholar 

  • Yamamoto A, Lucas JJ, Hen R (2000) Reversal of neuropathology and motor dysfunction in a conditional model of Huntington’s disease. Cell 101:57–66

    Article  CAS  PubMed  Google Scholar 

  • Yu T, Scully S, Yu Y, Fox GM, Jing S, Zhou R (1998) Expression of GDNF family receptor components during development: implications in the mechanisms of interaction. J Neurosci 18:4684–4696

    CAS  PubMed  Google Scholar 

  • Zinszner H, Kuroda M, Wang X, Batchvarova N, Lightfoot RT, Remotti H, Stevens JL, Ron D (1998) CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum. Genes Dev 12:982–995

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, The College of Physicians and Surgeons, Columbia University, 650 West 168th Street, New York, NY 10032, USA

    Robert E. Burke

  2. Department of Pathology, The College of Physicians and Surgeons, Columbia University, 650 West 168th Street, New York, NY 10032, USA

    Robert E. Burke

Authors
  1. Robert E. Burke
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert E. Burke.

Additional information

This work was supported by NS26836, NS38370, DAMD17-03-1-0492, and the Parkinson’s Disease Foundation

Rights and permissions

Reprints and permissions

About this article

Cite this article

Burke, R.E. Ontogenic cell death in the nigrostriatal system. Cell Tissue Res 318, 63–72 (2004). https://doi.org/10.1007/s00441-004-0908-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-004-0908-4

Keywords

Search

Navigation