Postnatal neuronal apoptosis in the cerebral cortex: Physiological and pathophysiological mechanisms

Neuroscience

Volumn 254, Issue , 2013, Pages 369-378

  Nikolic M ^a   Gardner, H A R ^b   Tucker, K L ^a  

^a UNIVERSITY OF HEIDELBERG   (Germany)

^b ASTRAZENECA   (United Kingdom)

Author keywords

Anesthetics; Apoptosis; Cerebral cortex; Ethanol; NMDA; RhoA

Indexed keywords

N METHYL DEXTRO ASPARTIC ACID RECEPTOR; RHOA GUANINE NUCLEOTIDE BINDING PROTEIN; RHOB GUANINE NUCLEOTIDE BINDING PROTEIN; SOMATOMEDIN C;

APOPTOSIS; BRAIN CORTEX; BRAIN DEVELOPMENT; BRAIN NERVE CELL; CENTRAL NERVOUS SYSTEM; ENZYME ACTIVITY; HUMAN; NERVE CELL NECROSIS; NERVE CELL NETWORK; NONHUMAN; PATHOPHYSIOLOGY; PERINATAL PERIOD; PERIPHERAL NERVOUS SYSTEM; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; ANIMAL; GROWTH, DEVELOPMENT AND AGING; NERVE CELL; PATHOLOGY; PHYSIOLOGY; SIGNAL TRANSDUCTION;

ANIMALS; APOPTOSIS; CEREBRAL CORTEX; HUMANS; NEURONS; SIGNAL TRANSDUCTION;

EID: 84887610874     PISSN: 03064522     EISSN: 18737544     Source Type: Journal    
DOI: 10.1016/j.neuroscience.2013.09.035     Document Type: Review

References (96)

1. Ahmed N.N., Grimes H.L., Bellacosa A., Chan T.O., Tsichlis P.N. Transduction of interleukin-2 antiapoptotic and proliferative signals via Akt protein kinase. Proc Natl Acad Sci U S A 1997, 94:3627-3632.
2. Alfonso-Loeches S., Guerri C. Molecular and behavioral aspects of the actions of alcohol on the adult and developing brain. Crit Rev Clin Lab Sci 2011, 48:19-47.
3. Arbour N., Vanderluit J.L., Le Grand J.N., Jahani-Asl A., Ruzhynsky V.A., Cheung E.C., Kelly M.A., MacKenzie A.E., Park D.S., Opferman J.T., Slack R.S. Mcl-1 is a key regulator of apoptosis during CNS development and after DNA damage. J Neurosci 2008, 28:6068-6078.
4. Barberan S., McNair K., Iqbal K., Smith N.C., Prendergast G.C., Stone T.W., Cobb S.R., Morris B.J. Altered apoptotic responses in neurons lacking RhoB GTPase. Eur J Neurosci 2011, 34:1737-1746.
5. Bibel M., Barde Y.A. Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system. Genes Dev 2000, 14:2919-2937.
6. Bittigau P., Sifringer M., Genz K., Reith E., Pospischil D., Govindarajalu S., Dzietko M., Pesditschek S., Mai I., Dikranian K., Olney J.W., Ikonomidou C. Antiepileptic drugs and apoptotic neurodegeneration in the developing brain. Proc Natl Acad Sci U S A 2002, 99:15089-15094.
7. Blaschke A.J., Staley K., Chun J. Widespread programmed cell death in proliferative and postmitotic regions of the fetal cerebral cortex. Development 1996, 122:1165-1174.
8. Blaschke A.J., Weiner J.A., Chun J. Programmed cell death is a universal feature of embryonic and postnatal neuroproliferative regions throughout the central nervous system. J Comp Neurol 1998, 396:39-50.
9. Brabeck C., Beschorner R., Conrad S., Mittelbronn M., Bekure K., Meyermann R., Schluesener H.J., Schwab J.M. Lesional expression of RhoA and RhoB following traumatic brain injury in humans. J Neurotrauma 2004, 21:697-706.
10. Brabeck C., Mittelbronn M., Bekure K., Meyermann R., Schluesener H.J., Schwab J.M. Effect of focal cerebral infarctions on lesional RhoA and RhoB expression. Arch Neurol 2003, 60:1245-1249.
11. Brodie M.J., Dichter M.A. Antiepileptic drugs. N England J Med 1996, 334:168-175.
12. Cecconi F., Alvarez-Bolado G., Meyer B.I., Roth K.A., Gruss P. Apaf1 (CED-4 homolog) regulates programmed cell death in mammalian development. Cell 1998, 94:727-737.
13. Chrysis D., Calikoglu A.S., Ye P., D'Ercole A.J. Insulin-like growth factor-I overexpression attenuates cerebellar apoptosis by altering the expression of Bcl family proteins in a developmentally specific manner. J Neurosci 2001, 21:1481-1489.
14. Climent E., Pascual M., Renau-Piqueras J., Guerri C. Ethanol exposure enhances cell death in the developing cerebral cortex: role of brain-derived neurotrophic factor and its signaling pathways. J Neurosci Res 2002, 68:213-225.
15. Conradt B. Genetic control of programmed cell death during animal development. Annu Rev Genet 2009, 43:493-523.
16. D'Mello S.R., Borodezt K., Soltoff S.P. Insulin-like growth factor and potassium depolarization maintain neuronal survival by distinct pathways: possible involvement of PI 3-kinase in IGF-1 signaling. J Neurosci 1997, 17:1548-1560.
17. Datta S.R., Dudek H., Tao X., Masters S., Fu H., Gotoh Y., Greenberg M.E. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 1997, 91:231-241.
18. Datta S.R., Katsov A., Hu L., Petros A., Fesik S.W., Yaffe M.B., Greenberg M.E. 14-3-3 proteins and survival kinases cooperate to inactivate BAD by BH3 domain phosphorylation. Mol Cell 2000, 6:41-51.
19. Davies A.M. Regulation of neuronal survival and death by extracellular signals during development. EMBO J 2003, 22:2537-2545.
20. Dobbing J., Sands J. Comparative aspects of the brain growth spurt. Early Hum Dev 1979, 3:79-83.
21. Dudek H., Datta S.R., Franke T.F., Birnbaum M.J., Yao R., Cooper G.M., Segal R.A., Kaplan D.R., Greenberg M.E. Regulation of neuronal survival by the serine-threonine protein kinase Akt. Science 1997, 275:661-665.
22. Dumas T.C. Developmental regulation of cognitive abilities: modified composition of a molecular switch turns on associative learning. Progress in neurobiology 2005, 76:189-211.
23. Ernfors P., Lee K.F., Jaenisch R. Mice lacking brain-derived neurotrophic factor develop with sensory deficits. Nature 1994, 368:147-150.
24. Etienne-Manneville S., Hall A. Rho GTPases in cell biology. Nature 2002, 420:629-635.
25. Ferrer I., Bernet E., Soriano E., del Rio T., Fonseca M. Naturally occurring cell death in the cerebral cortex of the rat and removal of dead cells by transitory phagocytes. Neuroscience 1990, 39:451-458.
26. Finlay B.L., Slattery M. Local differences in the amount of early cell death in neocortex predict adult local specializations. Science 1983, 219:1349-1351.
27. Fishbein I., Segal M. Miniature synaptic currents become neurotoxic to chronically silenced neurons. Cereb Cortex 2007, 17:1292-1306.
28. Franks N.P., Dickinson R., de Sousa S.L., Hall A.C., Lieb W.R. How does xenon produce anaesthesia?. Nature 1998, 396:324.
29. Ghosh A., Carnahan J., Greenberg M.E. Requirement for BDNF in activity-dependent survival of cortical neurons. Science 1994, 263:1618-1623.
30. Graumann W. Zelldegeneration im Telencephalon medium und Paraphysenentwicklung bei der weissen Maus. Z Anat EntwGesch 1950, 115:19-31.
31. Hakem R., Hakem A., Duncan G.S., Henderson J.T., Woo M., Soengas M.S., Elia A., de la Pompa J.L., Kagi D., Khoo W., Potter J., Yoshida R., Kaufman S.A., Lowe S.W., Penninger J.M., Mak T.W. Differential requirement for caspase 9 in apoptotic pathways in vivo. Cell 1998, 94:339-352.
32. Hamburger V., Levi-Montalcini R. Proliferation, differentiation and degeneration in the spinal ganglia of the chick embryo under normal and experimental conditions. J Exp Zool 1949, 111:457-501.
33. Hanganu I.L., Ben-Ari Y., Khazipov R. Retinal waves trigger spindle bursts in the neonatal rat visual cortex. J Neurosci 2006, 26:6728-6736.
34. Hardingham G.E., Fukunaga Y., Bading H. Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways. Nat Neurosci 2002, 5:405-414.
35. Haubensak W., Attardo A., Denk W., Huttner W.B. Neurons arise in the basal neuroepithelium of the early mammalian telencephalon: a major site of neurogenesis. Proc Natl Acad Sci U S A 2004, 101:3196-3201.
36. Heck N., Golbs A., Riedemann T., Sun J.J., Lessmann V., Luhmann H.J. Activity-dependent regulation of neuronal apoptosis in neonatal mouse cerebral cortex. Cereb Cortex 2008, 18:1335-1349.
37. Heumann D., Leuba G. Neuronal death in the development and aging of the cerebral cortex of the mouse. Neuropathol Appl Neurobiol 1983, 9:297-311.
38. Heumann D., Leuba G., Rabinowicz T. Postnatal development of the mouse cerebral neocortex. IV. Evolution of the total cortical volume, of the population of neurons and glial cells. J Hirnforschung 1978, 19:385-393.
39. Hodge R.D., D'Ercole A.J., O'Kusky J.R. Insulin-like growth factor-I accelerates the cell cycle by decreasing G1 phase length and increases cell cycle reentry in the embryonic cerebral cortex. J Neurosci 2004, 24:10201-10210.
40. Hodge R.D., D'Ercole A.J., O'Kusky J.R. Insulin-like growth factor-I (IGF-I) inhibits neuronal apoptosis in the developing cerebral cortex in vivo. Int J Dev Neurosci 2007, 25:233-241.
41. Horvitz H.R. Genetic control of programmed cell death in the nematode Caenorhabditis elegans. Cancer Res 1999, 59:1701s-1706s.
42. Ikonomidou C., Bittigau P., Ishimaru M.J., Wozniak D.F., Koch C., Genz K., Price M.T., Stefovska V., Horster F., Tenkova T., Dikranian K., Olney J.W. Ethanol-induced apoptotic neurodegeneration and fetal alcohol syndrome. Science 2000, 287:1056-1060.
43. Ikonomidou C., Bosch F., Miksa M., Bittigau P., Vockler J., Dikranian K., Tenkova T.I., Stefovska V., Turski L., Olney J.W. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science 1999, 283:70-74.
44. Jevtovic-Todorovic V., Hartman R.E., Izumi Y., Benshoff N.D., Dikranian K., Zorumski C.F., Olney J.W., Wozniak D.F. Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J Neurosci 2003, 23:876-882.
45. Jiang Y., de Bruin A., Caldas H., Fangusaro J., Hayes J., Conway E.M., Robinson M.L., Altura R.A. Essential role for survivin in early brain development. J Neurosci 2005, 25:6962-6970.
46. Kallen B. Cell degeneration during normal ontogenesis of the rabbit brain. J Anat 1955, 89:153-161.
47. Kennedy S.G., Wagner A.J., Conzen S.D., Jordan J., Bellacosa A., Tsichlis P.N., Hay N. The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal. Genes Dev 1997, 11:701-713.
48. Khazipov R., Sirota A., Leinekugel X., Holmes G.L., Ben-Ari Y., Buzsaki G. Early motor activity drives spindle bursts in the developing somatosensory cortex. Nature 2004, 432:758-761.
49. Kroemer G., Galluzzi L., Vandenabeele P., Abrams J., Alnemri E.S., Baehrecke E.H., Blagosklonny M.V., El-Deiry W.S., Golstein P., Green D.R., Hengartner M., Knight R.A., Kumar S., Lipton S.A., Malorni W., Nunez G., Peter M.E., Tschopp J., Yuan J., Piacentini M., Zhivotovsky B., Melino G. Classification of cell death: recommendations of the nomenclature committee on cell death 2009. Cell Death Differ 2009, 16:3-11.
50. Kuida K., Haydar T.F., Kuan C.Y., Gu Y., Taya C., Karasuyama H., Su M.S., Rakic P., Flavell R.A. Reduced apoptosis and cytochrome c-mediated caspase activation in mice lacking caspase 9. Cell 1998, 94:325-337.
51. Kuida K., Zheng T.S., Na S., Kuan C., Yang D., Karasuyama H., Rakic P., Flavell R.A. Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice. Nature 1996, 384:368-372.
52. Leveille F., El Gaamouch F., Gouix E., Lecocq M., Lobner D., Nicole O., Buisson A. Neuronal viability is controlled by a functional relation between synaptic and extrasynaptic NMDA receptors. FASEB J 2008, 22:4258-4271.
53. Ma D., Hossain M., Chow A., Arshad M., Battson R.M., Sanders R.D., Mehmet H., Edwards A.D., Franks N.P., Maze M. Xenon and hypothermia combine to provide neuroprotection from neonatal asphyxia. Ann Neurol 2005, 58:182-193.
54. Malatesta P., Hack M.A., Hartfuss E., Kettenmann H., Klinkert W., Kirchhoff F., Gotz M. Neuronal or glial progeny: regional differences in radial glia fate. Neuron 2003, 37:751-764.
55. McConnell M.J., MacMillan H.R., Chun J. Mathematical modeling supports substantial mouse neural progenitor cell death. Neural Dev 2009, 4:28.
56. Milh M., Kaminska A., Huon C., Lapillonne A., Ben-Ari Y., Khazipov R. Rapid cortical oscillations and early motor activity in premature human neonate. Cereb Cortex 2007, 17:1582-1594.
57. Miller T.M., Tansey M.G., Johnson E.M., Creedon D.J. Inhibition of phosphatidylinositol 3-kinase activity blocks depolarization- and insulin-like growth factor I-mediated survival of cerebellar granule cells. J Biol Chem 1997, 272:9847-9853.
58. Minambres R., Guasch R.M., Perez-Arago A., Guerri C. The RhoA/ROCK-I/MLC pathway is involved in the ethanol-induced apoptosis by anoikis in astrocytes. J Cell Sci 2006, 119:271-282.
59. Motoyama N., Wang F., Roth K.A., Sawa H., Nakayama K., Nakayama K., Negishi I., Senju S., Zhang Q., Fujii S., et al. Massive cell death of immature hematopoietic cells and neurons in Bcl-x-deficient mice. Science 1995, 267:1506-1510.
60. Naruse I., Keino H. Apoptosis in the developing CNS. Prog Neurobiol 1995, 47:135-155.
61. Nikoletopoulou V., Lickert H., Frade J.M., Rencurel C., Giallonardo P., Zhang L., Bibel M., Barde Y.A. Neurotrophin receptors TrkA and TrkC cause neuronal death whereas TrkB does not. Nature 2010, 467:59-63.
62. Olney J.W., Farber N.B., Wozniak D.F., Jevtovic-Todorovic V., Ikonomidou C. Environmental agents that have the potential to trigger massive apoptotic neurodegeneration in the developing brain. Environ Health Perspect 2000, 108(Suppl. 3):383-388.
63. Popken G.J., Hodge R.D., Ye P., Zhang J., Ng W., O'Kusky J.R., D'Ercole A.J. In vivo effects of insulin-like growth factor-I (IGF-I) on prenatal and early postnatal development of the central nervous system. Eur J Neurosci 2004, 19:2056-2068.
64. Poser S., Impey S., Xia Z., Storm D.R. Brain-derived neurotrophic factor protection of cortical neurons from serum withdrawal-induced apoptosis is inhibited by cAMP. J Neurosci 2003, 23:4420-4427.
65. Price D.J., Blakemore C. The postnatal development of the association projection from visual cortical area 17 to area 18 in the cat. J Neurosci 1985, 5:2443-2452.
66. Purves D. Body and brain: a trophic theory of neural connections 1990, Harvard University Press, Cambridge, MA, USA.
67. Qiu J., Tan Y.W., Hagenston A.M., Martel M.A., Kneisel N., Skehel P.A., Wyllie D.J., Bading H., Hardingham G.E. Mitochondrial calcium uniporter Mcu controls excitotoxicity and is transcriptionally repressed by neuroprotective nuclear calcium signals. Nat Commun 2013, 4:2034.
68. Rauskolb S., Zagrebelsky M., Dreznjak A., Deogracias R., Matsumoto T., Wiese S., Erne B., Sendtner M., Schaeren-Wiemers N., Korte M., Barde Y.A. Global deprivation of brain-derived neurotrophic factor in the CNS reveals an area-specific requirement for dendritic growth. J Neurosci 2010, 30:1739-1749.
69. Roth K.A., Kuan C., Haydar T.F., D'Sa-Eipper C., Shindler K.S., Zheng T.S., Kuida K., Flavell R.A., Rakic P. Epistatic and independent functions of caspase-3 and Bcl-X(L) in developmental programmed cell death. Proc Natl Acad Sci U S A 2000, 97:466-471.
70. Sanders R.D., Maze M. Xenon: from stranger to guardian. Curr Opin Anaesthesiol 2005, 18:405-411.
71. Sanno H (2007) The generation and characterization of transgenic mice expressing modifiers of Rho GTPases. In: Fakultät der Biowissenschaften, vol. Ph. D. Heidelberg: Universität Heidelberg.
72. Sanno H., Shen X., Kuru N., Bormuth I., Bobsin K., Gardner H.A.R.G., Komljenovic D., Tarabykin V., Erzurumlu R., Tucker K.L. Control of postnatal apoptosis in the neocortex by RhoA-subfamily GTPases determines neuronal density. J Neurosci 2010, 30:4221-4231.
73. Schweichel J.U., Merker H.J. The morphology of various types of cell death in prenatal tissues. Teratology 1973, 7:253-266.
74. Semenova M.M., Maki-Hokkonen A.M., Cao J., Komarovski V., Forsberg K.M., Koistinaho M., Coffey E.T., Courtney M.J. Rho mediates calcium-dependent activation of p38alpha and subsequent excitotoxic cell death. Nat Neurosci 2007, 10:436-443.
75. Shindler K.S., Latham C.B., Roth K.A. Bax deficiency prevents the increased cell death of immature neurons in bcl-x-deficient mice. J Neurosci 1997, 17:3112-3119.
76. Shindler K.S., Yunker A.M., Cahn R., Zha J., Korsmeyer S.J., Roth K.A. Trophic support promotes survival of bcl-x-deficient telencephalic cells in vitro. Cell Death Differ 1998, 5:901-910.
77. Shu Y., Zhou Z., Wan Y., Sanders R.D., Li M., Pac-Soo C.K., Maze M., Ma D. Nociceptive stimuli enhance anesthetic-induced neuroapoptosis in the rat developing brain. Neurobiol Dis 2012, 45:743-750.
78. Spreafico R., Frassoni C., Arcelli P., Selvaggio M., De Biasi S. In situ labeling of apoptotic cell death in the cerebral cortex and thalamus of rats during development. J Comp Neurol 1995, 363:281-295.
79. Stanika R.I., Pivovarova N.B., Brantner C.A., Watts C.A., Winters C.A., Andrews S.B. Coupling diverse routes of calcium entry to mitochondrial dysfunction and glutamate excitotoxicity. Proc Natl Acad Sci U S A 2009, 106:9854-9859.
80. Stewart C.E., Rotwein P. Growth, differentiation, and survival: multiple physiological functions for insulin-like growth factors. Physiol Rev 1996, 76:1005-1026.
81. Takadera T., Matsuda I., Ohyashiki T. Apoptotic cell death and caspase-3 activation induced by N-methyl-d-aspartate receptor antagonists and their prevention by insulin-like growth factor I. J Neurochem 1999, 73:548-556.
82. Talantova M., Sanz-Blasco S., Zhang X., Xia P., Akhtar M.W., Okamoto S., Dziewczapolski G., Nakamura T., Cao G., Pratt A.E., Kang Y.J., Tu S., Molokanova E., McKercher S.R., Hires S.A., Sason H., Stouffer D.G., Buczynski M.W., Solomon J.P., Michael S., Powers E.T., Kelly J.W., Roberts A., Tong G., Fang-Newmeyer T., Parker J., Holland E.A., Zhang D., Nakanishi N., Chen H.S., Wolosker H., Wang Y., Parsons L.H., Ambasudhan R., Masliah E., Heinemann S.F., Pina-Crespo J.C., Lipton S.A. Abeta induces astrocytic glutamate release, extrasynaptic NMDA receptor activation, and synaptic loss. Proc Natl Acad Sci U S A 2013, 110:E2518-2527.
83. Thomaidou D., Mione M.C., Cavanagh J.F., Parnavelas J.G. Apoptosis and its relation to the cell cycle in the developing cerebral cortex. J Neurosci 1997, 17:1075-1085.
84. Trapp T., Olah L., Holker I., Besselmann M., Tiesler C., Maeda K., Hossmann K.A. GTPase RhoB: an early predictor of neuronal death after transient focal ischemia in mice. Mol Cell Neurosci 2001, 17:883-894.
85. van den Eijnde S.M., Lips J., Boshart L., Vermeij-Keers C., Marani E., Reutelingsperger C.P., De Zeeuw C.I. Spatiotemporal distribution of dying neurons during early mouse development. Eur J Neurosci 1999, 11:712-724.
86. Verhage M., Maia A.S., Plomp J.J., Brussaard A.B., Heeroma J.H., Vermeer H., Toonen R.F., Hammer R.E., van den Berg T.K., Missler M., Geuze H.J., Sudhof T.C. Synaptic assembly of the brain in the absence of neurotransmitter secretion. Science 2000, 287:864-869.
87. Wagner-Golbs A., Luhmann H.J. Activity-dependent survival of developing neocortical neurons depends on PI3K signalling. J Neurochem 2012, 120:495-501.
88. Walz C., Jungling K., Lessmann V., Gottmann K. Presynaptic plasticity in an immature neocortical network requires NMDA receptor activation and BDNF release. J Neurophysiol 2006, 96:3512-3516.
89. Yang T., Zhuang L., Rei Fidalgo A.M., Petrides E., Terrando N., Wu X., Sanders R.D., Robertson N.J., Johnson M.R., Maze M., Ma D. Xenon and sevoflurane provide analgesia during labor and fetal brain protection in a perinatal rat model of hypoxia-ischemia. PLoS ONE 2012, 7:e37020.
90. Yoshida H., Kong Y.Y., Yoshida R., Elia A.J., Hakem A., Hakem R., Penninger J.M., Mak T.W. Apaf1 is required for mitochondrial pathways of apoptosis and brain development. Cell 1998, 94:739-750.
91. Zaidi A.U., D'Sa-Eipper C., Brenner J., Kuida K., Zheng T.S., Flavell R.A., Rakic P., Roth K.A. Bcl-X(L)-caspase-9 interactions in the developing nervous system: evidence for multiple death pathways. J Neurosci 2001, 21:169-175.
92. Zhang F.X., Rubin R., Rooney T.A. Ethanol induces apoptosis in cerebellar granule neurons by inhibiting insulin-like growth factor 1 signaling. J Neurochem 1998, 71:196-204.
93. Zhang F.X., Rubin R., Rooney T.A. N-methyl-d-aspartate inhibits apoptosis through activation of phosphatidylinositol 3-kinase in cerebellar granule neurons. A role for insulin receptor substrate-1 in the neurotrophic action of n-methyl-d-aspartate and its inhibition by ethanol. J Biol Chem 1998, 273:26596-26602.
94. Zhang S.J., Steijaert M.N., Lau D., Schutz G., Delucinge-Vivier C., Descombes P., Bading H. Decoding NMDA receptor signaling: identification of genomic programs specifying neuronal survival and death. Neuron 2007, 53:549-562.
95. Zhou Z.W., Shu Y., Li M., Guo X., Pac-Soo C., Maze M., Ma D. The glutaminergic, GABAergic, dopaminergic but not cholinergic neurons are susceptible to anaesthesia-induced cell death in the rat developing brain. Neuroscience 2011, 174:64-70.
96. Zimmerman L., Parr B., Lendahl U., Cunningham M., McKay R., Gavin B., Mann J., Vassileva G., McMahon A. Independent regulatory elements in the nestin gene direct transgene expression to neural stem cells or muscle precursors. Neuron 1994, 12:11-24.