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Previous Article | Next Article
Volume 17, Number 15, Issue of August 1, 1997 pp. 5820-5829
Copyright ©1997 Society for NeuroscienceEpidermal Growth Factor and Fibroblast Growth Factor-2 Have Different Effects on Neural Progenitors in the Adult Rat Brain
Received Dec. 11, 1996; revised March 27, 1997; accepted May 9, 1997.
H. Georg Kuhn1, Jürgen Winkler2, 3, Gerd Kempermann1, Leon J. Thal2, 3, and Fred H. Gage1 1 Laboratory of Genetics, The Salk Institute, La Jolla, California 92186, 2 Department of Neurosciences, University of California San Diego, La Jolla, California 92093, and 3 Neurology Service (127), Veterans Affairs Medical Center, La Jolla, California 92161
Neurons and glia are generated throughout adulthood from proliferating cells in two regions of the rat brain, the subventricular zone (SVZ) and the hippocampus. This study shows that exogenous basic fibroblast growth factor (FGF-2) and epidermal growth factor (EGF) have differential and site-specific effects on progenitor cells in vivo. Both growth factors expanded the SVZ progenitor population after 2 weeks of intracerebroventricular administration, but only FGF-2 induced an increase in the number of newborn cells, most prominently neurons, in the olfactory bulb, the normal destination for neuronal progenitors migrating from the SVZ. EGF, on the other hand, reduced the total number of newborn neurons reaching the olfactory bulb and substantially enhanced the generation of astrocytes in the olfactory bulb. Moreover, EGF increased the number of newborn cells in the striatum either by migration of SVZ cells or by stimulation of local progenitor cells. No evidence of neuronal differentiation of newborn striatal cells was found by three-dimensional confocal analysis, although many of these newborn cells were associated closely with striatal neurons. The proliferation of hippocampal progenitors was not affected by either growth factor. However, EGF increased the number of newborn glia and reduced the number of newborn neurons, similar to the effects seen in the olfactory bulb. These findings may be useful for elucidating the in vivo role of growth factors in neurogenesis in the adult CNS and may aid development of neuronal replacement strategies after brain damage.
Key words: subventricular zone; hippocampus; epidermal growth factor; basic fibroblast growth factor; intracerebroventricular administration; progenitor cells; stem cells; proliferation; neurogenesis; gliogenesis
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Neurogenesis in dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat
PNAS, April 10, 2001; 98(8): 4710 - 4715.
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D. R. Kornack and P. Rakic
The generation, migration, and differentiation of olfactory neurons in the adult primate brain
PNAS, April 10, 2001; 98(8): 4752 - 4757.
[Abstract] [Full Text] [PDF]
B.-S. Li, W. Ma, L. Zhang, J. L. Barker, D. A. Stenger, and H. C. Pant
Activation of Phosphatidylinositol-3 Kinase (PI-3K) and Extracellular Regulated Kinases (Erk1/2) Is Involved in Muscarinic Receptor-Mediated DNA Synthesis in Neural Progenitor Cells
J. Neurosci., March 1, 2001; 21(5): 1569 - 1579.
[Abstract] [Full Text] [PDF]
D. M. Allen, H. van Praag, J. Ray, Z. Weaver, C. J. Winrow, T. A. Carter, R. Braquet, E. Harrington, T. Ried, K. D. Brown, et al.
Ataxia telangiectasia mutated is essential during adult neurogenesis
Genes & Dev., March 1, 2001; 15(5): 554 - 566.
[Abstract] [Full Text]
L. S. Shihabuddin, P. J. Horner, J. Ray, and F. H. Gage
Adult Spinal Cord Stem Cells Generate Neurons after Transplantation in the Adult Dentate Gyrus
J. Neurosci., December 1, 2000; 20(23): 8727 - 8735.
[Abstract] [Full Text] [PDF]
F. M. Vaccarino
Stem Cells and Neuronal Progenitors and Their Diversity in the CNS: Are Time and Place Important?
Neuroscientist, October 1, 2000; 6(5): 338 - 352.
[Abstract] [PDF]
J. Liu, R. Bernabeu, A. Lu, and F. R. Sharp
Neurogenesis and Gliogenesis in the Postischemic Brain
Neuroscientist, October 1, 2000; 6(5): 362 - 370.
[Abstract] [PDF]
T. F. Haydar, F. Wang, M. L. Schwartz, and P. Rakic
Differential Modulation of Proliferation in the Neocortical Ventricular and Subventricular Zones
J. Neurosci., August 1, 2000; 20(15): 5764 - 5774.
[Abstract] [Full Text] [PDF]
D. R. Piper, T. Mujtaba, M. S. Rao, and M. T. Lucero
Immunocytochemical and Physiological Characterization of a Population of Cultured Human Neural Precursors
J Neurophysiol, July 1, 2000; 84(1): 534 - 548.
[Abstract] [Full Text] [PDF]
R. Raballo, J. Rhee, R. Lyn-Cook, J. F. Leckman, M. L. Schwartz, and F. M. Vaccarino
Basic Fibroblast Growth Factor (Fgf2) Is Necessary for Cell Proliferation and Neurogenesis in the Developing Cerebral Cortex
J. Neurosci., July 1, 2000; 20(13): 5012 - 5023.
[Abstract] [Full Text] [PDF]
F. H. Gage
Mammalian Neural Stem Cells
Science, February 25, 2000; 287(5457): 1433 - 1438.
[Abstract] [Full Text]
J. R. Murrell and D. D. Hunter
An Olfactory Sensory Neuron Line, Odora, Properly Targets Olfactory Proteins and Responds to Odorants
J. Neurosci., October 1, 1999; 19(19): 8260 - 8270.
[Abstract] [Full Text] [PDF]
T. D. Palmer, E. A. Markakis, A. R. Willhoite, F. Safar, and F. H. Gage
Fibroblast Growth Factor-2 Activates a Latent Neurogenic Program in Neural Stem Cells from Diverse Regions of the Adult CNS
J. Neurosci., October 1, 1999; 19(19): 8487 - 8497.
[Abstract] [Full Text] [PDF]
J. P. Wagner, I. B. Black, and E. DiCicco-Bloom
Stimulation of Neonatal and Adult Brain Neurogenesis by Subcutaneous Injection of Basic Fibroblast Growth Factor
J. Neurosci., July 15, 1999; 19(14): 6006 - 6016.
[Abstract] [Full Text] [PDF]
A. Gritti, P. Frolichsthal-Schoeller, R. Galli, E. A. Parati, L. Cova, S. F. Pagano, C. R. Bjornson, and A. L. Vescovi
Epidermal and Fibroblast Growth Factors Behave as Mitogenic Regulators for a Single Multipotent Stem Cell-Like Population from the Subventricular Region of the Adult Mouse Forebrain
J. Neurosci., May 1, 1999; 19(9): 3287 - 3297.
[Abstract] [Full Text] [PDF]
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