Development, Vol 120, Issue 2 301-311, Copyright © 1994 by Company of Biologists

JOURNAL ARTICLES

bcl-2 protein expression is widespread in the developing nervous system and retained in the adult PNS

DE Merry, DJ Veis, WF Hickey and SJ Korsmeyer
Department of Medicine and Pathology, Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, MO 63110.

Cell death is a common feature of neural development in all vertebrates. The bcl-2 proto-oncogene has been shown to protect a variety of cell types from programmed cell death. We have examined the distribution of bcl-2 protein in the developing and adult nervous systems. bcl-2 protein is widespread during embryonic development. Proliferating neuroepithelial cells of ventricular zones as well as the postmitotic cells of the cortical plate, cerebellum, hippocampus and spinal cord express bcl-2. Postnatally, bcl-2 is principally retained in the granule cells of the cerebellum and dentate gyrus of the hippocampus. bcl-2 expression in the CNS declines with aging. In the peripheral nervous system, neurons and supporting cells of sympathetic and sensory ganglia retain substantial bcl-2 protein throughout life. The widespread expression of bcl-2 in CNS and PNS neurons during embryonic development and its selective retention in the adult PNS is consistent with a role for bcl-2 in regulating neuronal survival. In addition, the expression of bcl-2 in some neuronal populations beyond the recognized period of cell death is suggestive of a role for bcl-2 beyond simply protecting neurons from developmental cell death.

This article has been cited by other articles:

				V. Degos, G. Loron, J. Mantz, and P. Gressens Neuroprotective Strategies for the Neonatal Brain Anesth. Analg., June 1, 2008; 106(6): 1670 - 1680. [Abstract] [Full Text] [PDF]

				J. Jodoin, S. Laroche-Pierre, C. G. Goodyer, and A. C. LeBlanc Defective Retrotranslocation Causes Loss of Anti-Bax Function in Human Familial Prion Protein Mutants J. Neurosci., May 9, 2007; 27(19): 5081 - 5091. [Abstract] [Full Text] [PDF]

				P Georges, E E Cornish, J M Provis, and M C Madigan Muller cell expression of glutamate cycle related proteins and anti-apoptotic proteins in early human retinal development Br. J. Ophthalmol., February 1, 2006; 90(2): 223 - 228. [Abstract] [Full Text] [PDF]

				W. -L. Kuan and R. A. Barker New Therapeutic Approaches to Parkinson's Disease Including Neural Transplants Neurorehabil Neural Repair, September 1, 2005; 19(3): 155 - 181. [Abstract] [PDF]

				K.-S. Cho, L. Yang, B. Lu, H. Feng Ma, X. Huang, M. Pekny, and D. F. Chen Re-establishing the regenerative potential of central nervous system axons in postnatal mice J. Cell Sci., March 1, 2005; 118(5): 863 - 872. [Abstract] [Full Text] [PDF]

				S. J. Vannucci and H. Hagberg Hypoxia-ischemia in the immature brain J. Exp. Biol., August 15, 2004; 207(18): 3149 - 3154. [Abstract] [Full Text] [PDF]

				J.-W. Shim, H.-C. Koh, M.-Y. Chang, E. Roh, C.-Y. Choi, Y. J. Oh, H. Son, Y.-S. Lee, L. Studer, and S.-H. Lee Enhanced In Vitro Midbrain Dopamine Neuron Differentiation, Dopaminergic Function, Neurite Outgrowth, and 1-Methyl-4-Phenylpyridium Resistance in Mouse Embryonic Stem Cells Overexpressing Bcl-XL J. Neurosci., January 28, 2004; 24(4): 843 - 852. [Abstract] [Full Text] [PDF]

				W. Peng, G. Henderson, G.-C. Perng, A. B. Nesburn, S. L. Wechsler, and C. Jones The Gene That Encodes the Herpes Simplex Virus Type 1 Latency-Associated Transcript Influences the Accumulation of Transcripts (Bcl-xL and Bcl-xS) That Encode Apoptotic Regulatory Proteins J. Virol., October 1, 2003; 77(19): 10714 - 10718. [Abstract] [Full Text] [PDF]

				X. Huang, D.-Y. Wu, G. Chen, H. Manji, and D. F. Chen Support of Retinal Ganglion Cell Survival and Axon Regeneration by Lithium through a Bcl-2-Dependent Mechanism Invest. Ophthalmol. Vis. Sci., January 1, 2003; 44(1): 347 - 354. [Abstract] [Full Text] [PDF]

				X.-H. Liu, R. J. Collier, and R. J. Youle Inhibition of Axotomy-induced Neuronal Apoptosis by Extracellular Delivery of a Bcl-XL Fusion Protein J. Biol. Chem., November 30, 2001; 276(49): 46326 - 46332. [Abstract] [Full Text] [PDF]

				R. Seidl, B. Bidmon, M. Bajo, B. C. Yoo, N. Cairns, E. C. LaCasse, and G. Lubec Evidence for Apoptosis in the Fetal Down Syndrome Brain J Child Neurol, June 1, 2001; 16(6): 438 - 442. [Abstract] [PDF]

				G Middleton, S Wyatt, N Ninkina, and A. Davies Reciprocal developmental changes in the roles of Bcl-w and Bcl-x(L) in regulating sensory neuron survival Development, January 2, 2001; 128(3): 447 - 457. [Abstract] [PDF]

				C D'Sa-Eipper, J. Leonard, G Putcha, T. Zheng, R. Flavell, P Rakic, K Kuida, and K. Roth DNA damage-induced neural precursor cell apoptosis requires p53 and caspase 9 but neither Bax nor caspase 3 Development, January 1, 2001; 128(1): 137 - 146. [Abstract] [PDF]

				C. Wang, J. A. Kaufmann, M. G. Sanchez-Ross, and K. M. Johnson Mechanisms of N-Methyl-D-aspartate-Induced Apoptosis in Phencyclidine-Treated Cultured Forebrain Neurons J. Pharmacol. Exp. Ther., July 1, 2000; 294(1): 287 - 295. [Abstract] [Full Text]

				W.-Y. Chan, K.-K. Cheung, J. O. Schorge, L.-W. Huang, W. R. Welch, D. A. Bell, R. S. Berkowitz, and S. C. Mok Bcl-2 and p53 Protein Expression, Apoptosis, and p53 Mutation in Human Epithelial Ovarian Cancers Am. J. Pathol., February 1, 2000; 156(2): 409 - 417. [Abstract] [Full Text] [PDF]

				M. K. Houseweart and D. W. Cleveland Bcl-2 Overexpression Does Not Protect Neurons from Mutant Neurofilament-Mediated Motor Neuron Degeneration J. Neurosci., August 1, 1999; 19(15): 6446 - 6456. [Abstract] [Full Text] [PDF]

				E. J. Coulson, K. Reid, G. L. Barrett, and P. F. Bartlett p75 Neurotrophin Receptor-mediated Neuronal Death Is Promoted by Bcl-2 and Prevented by Bcl-xL J. Biol. Chem., June 4, 1999; 274(23): 16387 - 16391. [Abstract] [Full Text] [PDF]

				C. G. Print, K. L. Loveland, L. Gibson, T. Meehan, A. Stylianou, N. Wreford, D. de Kretser, D. Metcalf, F. Kontgen, J. M. Adams, et al. Apoptosis regulator Bcl-w is essential for spermatogenesis but appears otherwise redundant PNAS, October 13, 1998; 95(21): 12424 - 12431. [Abstract] [Full Text] [PDF]

				M. D. Smith, E. A. Ensor, R. S. Coffin, L. M. Boxer, and D. S. Latchman Bcl-2 Transcription from the Proximal P2 Promoter Is Activated in Neuronal Cells by the Brn-3a POU Family Transcription Factor J. Biol. Chem., July 3, 1998; 273(27): 16715 - 16722. [Abstract] [Full Text] [PDF]

				G. Middleton, L. G. P. Pinon, S. Wyatt, and A. M. Davies Bcl-2 Accelerates the Maturation of Early Sensory Neurons J. Neurosci., May 1, 1998; 18(9): 3344 - 3350. [Abstract] [Full Text] [PDF]

				P. J. Bernier and A. Parent Bcl-2 Protein as a Marker of Neuronal Immaturity in Postnatal Primate Brain J. Neurosci., April 1, 1998; 18(7): 2486 - 2497. [Abstract] [Full Text] [PDF]

				U. Blomer, T. Kafri, L. Randolph-Moore, I. M. Verma, and F. H. Gage Bcl-xL protects adult septal cholinergic neurons from axotomized cell death PNAS, March 3, 1998; 95(5): 2603 - 2608. [Abstract] [Full Text] [PDF]

				A. Sh. Parsadanian, Y. Cheng, C. R. Keller-Peck, D. M. Holtzman, and W. D. Snider Bcl-xL is an Antiapoptotic Regulator for Postnatal CNS Neurons J. Neurosci., February 1, 1998; 18(3): 1009 - 1019. [Abstract] [Full Text] [PDF]

				H. S. Zanjani, M. W. Vogel, J. C. Martinou, N. Delhaye-Bouchaud, and J. Mariani Postnatal Expression of Hu-Bcl-2 Gene in Lurcher Mutant Mice Fails to Rescue Purkinje Cells but Protects Inferior Olivary Neurons from Target-Related Cell Death J. Neurosci., January 1, 1998; 18(1): 319 - 327. [Abstract] [Full Text] [PDF]

				M. Deshmukh and E. M. Johnson Jr. Programmed Cell Death in Neurons: Focus on the Pathway of Nerve Growth Factor Deprivation-Induced Death of Sympathetic Neurons Mol. Pharmacol., June 1, 1997; 51(6): 897 - 906. [Abstract] [Full Text]

				Y. Matsuzaki, K.-i. Nakayama, K. Nakayama, T. Tomita, M. Isoda, D. Y. Loh, and H. Nakauchi Role of bcl-2 in the Development of Lymphoid Cells From the Hematopoietic Stem Cell Blood, February 1, 1997; 89(3): 853 - 862. [Abstract] [Full Text] [PDF]

				L. Pinon, G Middleton, and A. Davies Bcl-2 is required for cranial sensory neuron survival at defined stages of embryonic development Development, January 10, 1997; 124(20): 4173 - 4178. [Abstract] [PDF]

				K Vekrellis, M. McCarthy, A Watson, J Whitfield, L. Rubin, and J Ham Bax promotes neuronal cell death and is downregulated during the development of the nervous system Development, January 3, 1997; 124(6): 1239 - 1249. [Abstract] [PDF]

				J. R. Singleton, V. M. Dixit, and E. L. Feldman Type I Insulin-like Growth Factor Receptor Activation Regulates Apoptotic Proteins J. Biol. Chem., December 13, 1996; 271(50): 31791 - 31794. [Abstract] [Full Text] [PDF]

				L. Bonfanti, E. Strettoi, S. Chierzi, M. C. Cenni, X.-H. Liu, J.-C. Martinou, L. Maffei, and S. A. Rabacchi Protection of Retinal Ganglion Cells from Natural and Axotomy-Induced Cell Death in Neonatal Transgenic Mice Overexpressing bcl-2 J. Neurosci., July 1, 1996; 16(13): 4186 - 4194. [Abstract] [Full Text] [PDF]

				R. S. Duman, V. A. Vaidya, M. Nibuya, S. Morinobu, and L. R. Fitzgerald Review : Stress, Antidepressant Treatments, and Neurotrophic Factors: Molecular and Cellular Mechanisms Neuroscientist, November 1, 1995; 1(6): 351 - 360. [Abstract] [PDF]

				C. M. Knudson, K. S. K. Tung, W. G. Tourtellotte, G. A. J. Brown, and S. J. Korsmeyer Bax-Deficient Mice with Lymphoid Hyperplasia and Male Germ Cell Death Science, October 6, 1995; 270(5233): 96 - 99. [Abstract] [PDF]

				N Motoyama, F Wang, K. Roth, H Sawa, K Nakayama, K Nakayama, I Negishi, S Senju, Q Zhang, S Fujii, et al. Massive cell death of immature hematopoietic cells and neurons in Bcl-x-deficient mice Science, March 10, 1995; 267(5203): 1506 - 1510. [Abstract] [PDF]

				S Kumar, M Kinoshita, M Noda, N G Copeland, and N A Jenkins Induction of apoptosis by the mouse Nedd2 gene, which encodes a protein similar to the product of the Caenorhabditis elegans cell death gene ced-3 and the mammalian IL-1 beta-converting enzyme. Genes & Dev., July 15, 1994; 8(14): 1613 - 1626. [Abstract] [PDF]

				M Gonzalez-Garcia, R Perez-Ballestero, L Ding, L Duan, L. Boise, C. Thompson, and G Nunez bcl-XL is the major bcl-x mRNA form expressed during murine development and its product localizes to mitochondria Development, January 10, 1994; 120(10): 3033 - 3042. [Abstract] [PDF]

				X.-M. Yin, Z.N. Oltvai, D.J. Veis-Novack, G.P. Linette, and S.J. Korsmeyer Bcl-2 Gene Family and the Regulation of Programmed Cell Death Cold Spring Harb Symp Quant Biol, January 1, 1994; 59(0): 387 - 393. [Abstract] [PDF]