 |
 Previous Article | Next Article 
Journal of Neuroscience, Vol 15, 2656-2667, Copyright © 1995 by Society for Neuroscience
Neurotrophin-4/5 (NT-4/5) and brain-derived neurotrophic factor (BDNF) act at later stages of cerebellar granule cell differentiation
WQ Gao, JL Zheng and M Karihaloo
Department of Neuroscience, Genentech, Inc., South San Francisco, California 94080, USA.
The developing cerebellum expresses genes which encode for both
neurotrophins and their receptors. The present study was designed to
determine at what stages during cerebellar granule cell neurogenesis
neurotrophin family molecules may act. We report here that in purified,
well-characterized granule cell cultures (Gao et al., 1991; 1992), none of
the neurotrophins stimulated proliferation of granule cell precursors or
rescued phenotypic defect of mutant weaver granule cell precursors in the
initiation of neuronal differentiation. However, neurotrophin-4/5 (NT-4/5)
and BDNF, but not neurotrophin-3 (NT-3) or NGF, promoted neurite extension
and survival of differentiated cerebellar granule cells. Both of these
effects were blocked by the specific inhibitor for Trk tyrosine kinases,
K-252a. NT-4/5 and BDNF also enhanced neurite extension by weaver granule
cells which were rescued by wild-type granule cells during differentiation.
Moreover, TrkB immunohistochemistry performed on sections of the developing
wildtype and weaver cerebella revealed that only differentiated granule
cells, but not the precursor cells, make high levels of TrkB receptor.
These findings together suggest that NT-4/5 and BDNF promote the maturation
and maintenance of differentiated granule cells, effects which are
downstream to the weaver gene. Since no additive effects were seen with the
combination of NT-4/5 and BDNF, it seems likely that the two neurotrophins
activate the same receptor trkB for signal transduction.
This article has been cited by other articles:
|
|
|
|
 
T. Koontz, M. Bralic, J. Tomac, E. Pernjak-Pugel, G. Bantug, S. Jonjic, and W. J. Britt
Altered development of the brain after focal herpesvirus infection of the central nervous system
J. Exp. Med.,
February 18, 2008;
205(2):
423 - 435.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. M. Johnson, E. T. Craig, and H. H. Yeh
TrkB is necessary for pruning at the climbing fibre-Purkinje cell synapse in the developing murine cerebellum
J. Physiol.,
July 15, 2007;
582(2):
629 - 646.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Furutani, Y. Okubo, S. Kakizawa, and M. Iino
Postsynaptic inositol 1,4,5-trisphosphate signaling maintains presynaptic function of parallel fiber-Purkinje cell synapses via BDNF
PNAS,
May 30, 2006;
103(22):
8528 - 8533.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Choi, P. R. Borghesani, J. A. Chan, and R. A. Segal
Migration from a Mitogenic Niche Promotes Cell-Cycle Exit
J. Neurosci.,
November 9, 2005;
25(45):
10437 - 10445.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Lu, Y. Wu, N. Sousa, and O. F. X. Almeida
SMAD pathway mediation of BDNF and TGF{beta}2 regulation of proliferation and differentiation of hippocampal granule neurons
Development,
July 15, 2005;
132(14):
3231 - 3242.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. L. Fiszman, A. Barberis, C. Lu, Z. Fu, F. Erdelyi, G. Szabo, and S. Vicini
NMDA Receptors Increase the Size of GABAergic Terminals and Enhance GABA Release
J. Neurosci.,
February 23, 2005;
25(8):
2024 - 2031.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Sadakata, A. Mizoguchi, Y. Sato, R. Katoh-Semba, M. Fukuda, K. Mikoshiba, and T. Furuichi
The Secretory Granule-Associated Protein CAPS2 Regulates Neurotrophin Release and Cell Survival
J. Neurosci.,
January 7, 2004;
24(1):
43 - 52.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Shalizi, M. Lehtinen, B. Gaudilliere, N. Donovan, J. Han, Y. Konishi, and A. Bonni
Characterization of a Neurotrophin Signaling Mechanism that Mediates Neuron Survival in a Temporally Specific Pattern
J. Neurosci.,
August 13, 2003;
23(19):
7326 - 7336.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. R. Borghesani, J. M. Peyrin, R. Klein, J. Rubin, A. R. Carter, P. M. Schwartz, A. Luster, G. Corfas, and R. A. Segal
BDNF stimulates migration of cerebellar granule cells
Development,
March 5, 2003;
129(6):
1435 - 1442.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Hirai and T. Launey
The Regulatory Connection between the Activity of Granule Cell NMDA Receptors and Dendritic Differentiation of Cerebellar Purkinje Cells
J. Neurosci.,
July 15, 2000;
20(14):
5217 - 5224.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Wagner, K. D. Wagner, M. Sefton, A. Rodríguez–Tébar, and R. Grantyn
An Abnormal Response of Retinoblastoma Cells (Y-79) to Neurotrophins
Invest. Ophthalmol. Vis. Sci.,
June 1, 2000;
41(7):
1932 - 1939.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
S. Bao, L. Chen, X. Qiao, and R. F. Thompson
Transgenic Brain-Derived Neurotrophic Factor Modulates a Developing Cerebellar Inhibitory Synapse
Learn. Mem.,
May 1, 1999;
6(3):
276 - 283.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
A. Shimada, C. A. Mason, and M. E. Morrison
TrkB Signaling Modulates Spine Density and Morphology Independent of Dendrite Structure in Cultured Neonatal Purkinje Cells
J. Neurosci.,
November 1, 1998;
18(21):
8559 - 8570.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Qiao, L. Chen, H. Gao, S. Bao, F. Hefti, R. F. Thompson, and B. Knusel
Cerebellar Brain-Derived Neurotrophic Factor-TrkB Defect Associated with Impairment of Eyeblink Conditioning in Stargazer Mutant Mice
J. Neurosci.,
September 1, 1998;
18(17):
6990 - 6999.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. E. Morrison and C. A. Mason
Granule Neuron Regulation of Purkinje Cell Development: Striking a Balance Between Neurotrophin and Glutamate Signaling
J. Neurosci.,
May 15, 1998;
18(10):
3563 - 3573.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. R. Mellor, D. Merlo, A. Jones, W. Wisden, and A. D. Randall
Mouse Cerebellar Granule Cell Differentiation: Electrical Activity Regulates the GABAA Receptor alpha 6 Subunit Gene
J. Neurosci.,
April 15, 1998;
18(8):
2822 - 2833.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Arsenijevic and S. Weiss
Insulin-Like Growth Factor-I Is a Differentiation Factor for Postmitotic CNS Stem Cell-Derived Neuronal Precursors: Distinct Actions from Those of Brain-Derived Neurotrophic Factor
J. Neurosci.,
March 15, 1998;
18(6):
2118 - 2128.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N Soussi-Yanicostas, C Faivre-Sarrailh, J. Hardelin, J Levilliers, G Rougon, and C Petit
Anosmin-1 underlying the X chromosome-linked Kallmann syndrome is an adhesion molecule that can modulate neurite growth in a cell-type specific manner
J. Cell Sci.,
January 10, 1998;
111(19):
2953 - 2965.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J. L. Zheng and W.-Q. Gao
Analysis of Rat Vestibular Hair Cell Development and Regeneration Using Calretinin as an Early Marker
J. Neurosci.,
November 1, 1997;
17(21):
8270 - 8282.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. J. Courtney, K. E. O. Akerman, and E. T. Coffey
Neurotrophins Protect Cultured Cerebellar Granule Neurons against the Early Phase of Cell Death by a TwoComponent Mechanism
J. Neurosci.,
June 1, 1997;
17(11):
4201 - 4211.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Rosario, B. Yandava, B Kosaras, D Zurakowski, R. Sidman, and E. Snyder
Differentiation of engrafted multipotent neural progenitors towards replacement of missing granule neurons in meander tail cerebellum may help determine the locus of mutant gene action
Development,
January 11, 1997;
124(21):
4213 - 4224.
[Abstract]
[PDF]
|
|
|
|
|
|
|
J. L. Zheng, C. Helbig, and W.-Q. Gao
Induction of Cell Proliferation by Fibroblast and Insulin-Like Growth Factors in Pure Rat Inner Ear Epithelial Cell Cultures
J. Neurosci.,
January 1, 1997;
17(1):
216 - 226.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L Minichiello and R Klein
TrkB and TrkC neurotrophin receptors cooperate in promoting survival of hippocampal and cerebellar granule neurons.
Genes & Dev.,
November 15, 1996;
10(22):
2849 - 2858.
[Abstract]
[PDF]
|
|
|
|
|
|
|
R. A. Segal, A. Bhattacharyya, L. A. Rua, J. A. Alberta, R. M. Stephens, D. R. Kaplan, and C. D. Stiles
Differential Utilization of Trk Autophosphorylation Sites
J. Biol. Chem.,
August 16, 1996;
271(33):
20175 - 20181.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. P. Henderson, L. Lin, A. Prasad, C. A. Paul, T. Y. Chang, and R. A. Maue
Embryonic Striatal Neurons from Niemann-Pick Type C Mice Exhibit Defects in Cholesterol Metabolism and Neurotrophin Responsiveness
J. Biol. Chem.,
June 23, 2000;
275(26):
20179 - 20187.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
