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The Journal of Neuroscience, April 1, 2003, 23(7):2804
A Chondroitin Sulfate Proteoglycan PTP
/RPTP
Regulates the Morphogenesis of Purkinje Cell Dendrites in the Developing Cerebellum
Masahiko Tanaka1, Nobuaki Maeda2, 3, Masaharu Noda2, and Tohru Marunouchi1 1 Division of Cell Biology, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan, 2 National Institute for Basic Biology, Graduate University for Advanced Studies, Okazaki, Aichi 444-8585, Japan, and 3 Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo 183-8526, Japan
ABSTRACT
TOP
ABSTRACT
Introduction
PTP
/RPTP
, a receptor-type protein tyrosine phosphatase synthesized as a chondroitin sulfate (CS) proteoglycan, uses a heparin-binding growth factor pleiotrophin (PTN) as a ligand, in which the CS portion plays an essential role in ligand binding. Using an organotypic slice culture system, we tested the hypothesis that PTN-PTP
Key words: PTP
Introduction
Neurons are characterized by the specific morphology of dendritic trees and axons, which are essential for information processing. Although the molecular mechanisms of directed axonal outgrowth are beginning to be elucidated, those underlying the morphogenesis of dendritic trees are poorly understood. Among the neurons of the CNS, the cerebellar Purkinje cells have the most elaborate dendritic trees. Mature Purkinje cells have a single primary dendrite, which extends toward the pial surface, branches extensively in the molecular layer (ML), and makes synaptic contacts with parallel fibers, the axons of granule cells. The presence and differentiation of granule cells are necessary for normal development of Purkinje cell dendrites, as shown in agranular cerebella of x-irradiated and mutant animals (Altman and Anderson, 1972
; Rakic and Sidman, 1973
Phosphacan/6B4 proteoglycan, a chondroitin sulfate (CS) proteoglycan expressed predominantly in the CNS, is distributed around the cell surface of Purkinje cells during dendritic outgrowth (Maeda et al., 1992
In this study, we hypothesized that PTN-PTP
Materials and Methods
Slice culture. The methods for slice culture have been described previously (Tanaka et al., 1994
6B4PG) against the extracellular domain of PTP
Analysis of the Purkinje cell morphology. For immunohistochemistry of inositol 1,4,5-trisphosphate receptor (IP3R), cerebellar slice cultures were fixed with 4% paraformaldehyde in CMF-PBS for 20 min at room temperature. For analysis of the cerebellum in vivo, 250-µm-thick slices were prepared from the vermes of the cerebella of 9- or 15-d-old rats and fixed as mentioned above. The slices were preincubated for 30 min in 10% normal goat serum and 0.3% Triton X-100 in CMF-PBS and then incubated overnight at 4°C in CMF-PBS containing a rat anti-mouse IP3R monoclonal antibody (4C11; 1:20) (Maeda et al., 1989
Immunohistochemistry of cryosections. For immunohistochemical analysis of IP3R, PTP
Quantitative analysis of Purkinje and granule cells and Bergmann fibers. For measurement of the length of the longest dendrite per cell and counting the number of dendritic branching points per cell, the stacked confocal microscopic images of Purkinje cells obtained as described above were analyzed using the LSM Ver. 2.8 software (Zeiss). For evaluation of the density of Purkinje and granule cells, cryosections of slice cultures were stained by immunohistochemistry using antibodies against IP3R and NeuN as described above. The IP3R- and NeuN-positive cells within 150 µm of the Purkinje cell layer (PL) and internal granular layer (IGL) were enumerated to determine the density of Purkinje and granule cells, respectively, in confocal microscopic images of 2-µm-thick optical sections. As another type of evaluation of granule cell density, the number of NeuN-positive cells within square areas of 100 × 100 µm2 of the IGL was counted. We did these two types of evaluation of granule cell density because migration of these cells from the EGL to the IGL might result in an increase of only one of the number of granule cells per unit length of the IGL and that per unit area of the IGL in slice cultures. When counting the NeuN-positive cells, the cells >10 µm in diameter (<0.1% of total NeuN-positive cells in the IGL) were not included because they might be Golgi cells. For evaluation of Bergmann fibers, GFAP-positive fibers >30 µm within 150 µm of the ML were enumerated in confocal microscopic images of 3-µm-thick optical sections. Statistical analysis was done using Student's t test.
Western blotting. Slice culture and treatment with Chase ABC or CS chains were done as described above. Three cultured slices at 3 DIV were combined and rapidly frozen on dry ice. The frozen slices were homogenized in 200 µl of 1% NP-40, 0.1% SDS, 2 mM phenylmethylsulfonyl fluoride, 1.5 µM aprotinin, 30 µM E64, 40 µM leupeptin, 100 µM bestatin, and 20 µM pepstatin A. After centrifugation at 15,000 × g for 15 min at 4°C, the supernatants (15 µg protein) were applied to 12.5% SDS-PAGE and Western blotting using a goat anti-PTN antibody (R&D systems, Minneapolis, MN; 1:1,000). The density of the bands was quantified by an Epson desktop scanner (GT-9700F) using NIH image software.
Results
Comparison of the morphogenesis of Purkinje cell dendrites in vivo and in slice cultures
In the present study, we examined the morphogenesis of Purkinje cell dendrites in postnatal cerebellar development using an organotypic slice culture system of cerebellum from 9-d-old rats (Tanaka et al., 1994
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Figure 1. Morphogenesis of Purkinje cell dendrites in vivo and in slice cultures. A-C, Fluorescent immunohistochemistry using a monoclonal antibody against IP3R (4C11) showing the morphology of Purkinje cells in the cerebellum from P9 (A, B) and P15 (C) rats. A, Low-power view of an immunostained cryosection. B, C, Confocal microscopic images of immunostained slices. The multiple primary dendrite (MPD)-type (arrows) and single primary dendrite (SPD)-type Purkinje cells coexist on P9 (B), whereas most Purkinje cells are of the SPD type on P15 (C). D-F, Overview (D) and fluorescent immunohistochemistry using 4C11 (E, F) of cerebellar slices derived from P9 rats and cultured for 6 d under control conditions. E, Low-power view of an immunostained cryosection. F, A confocal microscopic image of an immunostained slice culture. Scale bars: (in A) A, E, 100 µm; (in B) B, C, F, 25 µm; D, 1 mm. G, Quantitative representation of the ratios of the three types of Purkinje cells in vivo (P9 and P15) and in slice cultures at 6 DIV under control conditions. The ratio of SPD-type Purkinje cells significantly increased in slice cultures at 6 DIV compared with that on P9, although the increase was not as marked as in vivo. Cell counts were made in slices, not in cryosections, which enabled us to reliably distinguish the morphology of Purkinje cell dendrites. DOPD, Disoriented primary dendrite. n = 4. Error bars represent SEM. *p < 0.05, **p < 0.001 versus P9.
The morphology of Purkinje cell dendrites changes dramatically during postnatal cerebellar development (Hendelman and Aggerwal, 1980
Our slice culture system preserves the overall structure of cerebellar slices (Fig. 1D) and the cytoarchitecture of the cerebellar cortex and reproduces the serial process of granule cell development, including proliferation, migration, and extension of parallel fibers within 6 DIV, as described previously (Tanaka et al., 1994
As the first step in the present study, we carefully observed the morphological changes of Purkinje cell dendrites in vivo and in slice cultures under control conditions. The immunohistochemical analysis was done using slices, not sections (cryosections or paraffin sections) of slices, which enabled us to reliably distinguish the morphology of Purkinje cell dendrites. The morphology of Purkinje cells was classified into three types: single primary dendrite (SPD), multiple primary dendrite (MPD), and disoriented primary dendrite (DOPD). The MPD type was defined as Purkinje cells with multiple primary dendrites, all of which extended toward the pial surface. The DOPD type was defined as Purkinje cells with multiple primary dendrites, at least some of which had an abnormal orientation, for example, extending horizontally in the PL or downward into the IGL. No Purkinje cells with a single primary dendrite extending abnormally were observed in the present study.
In the rat cerebellum on postnatal day (P) 9, approximately half (47.9%) of the Purkinje cells were of the SPD type and half (49.6%) were of the MPD type (Fig. 1B,G). Few (2.5%) Purkinje cells were of the DOPD type. On P15, most Purkinje cells showed the SPD-type morphology (SPD/MPD/DOPD = 88.3:11.7:0.0%) (Fig. 1C,G). Also in our slice culture system, the ratio of SPD-type Purkinje cells significantly increased at 6 DIV compared with that on P9 (0 DIV), although somewhat fewer SPD-type and more MPD-type cells were observed under the culture conditions than in the P15 cerebellum (SPD/MPD/DOPD = 62.7:34.5:2.8%) (Fig. 1F,G). These results indicated that nearly normal morphological changes of Purkinje cell dendrites occur in our slice cultures under control conditions, although these changes appeared to proceed insufficiently in vitro.
Expression patterns of PTP
The expression pattern of PTP
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Figure 2. Expression patterns of PTP
During postnatal development of the cerebellum in vivo, differentiating dendrites of Purkinje cells are surrounded by the lamellate processes of Bergmann glia, which express GLAST, a glial glutamate transporter (Yamada et al., 2000
Immunohistochemical analysis using an antibody against PTN revealed that this growth factor shows a characteristic localization in the developing cerebellum (Fig. 2D-F). PTN was distributed abundantly in the ML and moderately in the IGL (Fig. 2E). Thus, signal transduction of PTP
Involvement of PTP
From the abundant expression of PTP
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Figure 3. Involvement of PTP
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Table 1. Quantitative evaluation of the growth of Purkinje cell dendrites and the density of Purkinje cells Consistently, sodium vanadate and phenylarsine oxide, protein tyrosine phosphatase inhibitors, also increased the MPD and DOPD types of Purkinje cells at 6 DIV [SPD/MPD/DOPD = 25.4:63.3:11.4% (sodium vanadate; 10 µM); 25.1:64.3:10.7% (phenylarsine oxide; 0.1 µM)] (Fig. 3D-F). We cannot exclude the possibility that these treatments retarded Purkinje cell development, however, because they concomitantly resulted in reduced extension and branching of Purkinje cell dendrites [longest dendrite per cell = 64.8 ± 3.1 µm (n = 41), branching points per cell = 40.8 ± 6.0 (n = 16) under vanadate-added (compare Table 1)].
Involvement of CS and PTN in the morphogenesis of Purkinje cell dendrites
CS plays essential roles in the signal transduction of PTP
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Figure 4. Involvement of chondroitin sulfate (CS) and PTN in the morphogenesis of Purkinje cell dendrites. A, B, Distribution of CS in the control (A) and chondroitinase ABC (Chase ABC)-treated (B) slice cultures. Cryosections of cerebellar slices derived from P9 rats, cultured for 6 d without (A) or with (B) Chase ABC (200 mU/ml), and stained by immunohistochemistry using a monoclonal antibody against CS (CS-56). Scale bar, 25 µm. C-J, Effects of Chase ABC, CS, and PTN on the morphogenesis of Purkinje cell dendrites. Shown are confocal microscopic images of cerebellar slices cultured for 6 d with culture medium containing Chase ABC (200 mU/ml) (C, D), CS-C (50 µg/ml) (E, F), CS-A (50 µg/ml) (G, H), and PTN (1 µg/ml) (I, J), and stained by fluorescent immunohistochemistry using 4C11. On addition of Chase ABC, CS-C, and PTN, the MPD (C, E, I) and DOPD (D, F, J) types of Purkinje cells increased. In contrast, many Purkinje cells had an SPD under the CS-A-added conditions (G, H). Scale bar, 25 µm. K, L, High-power views of the enclosed areas in D, H. Spine formation on Purkinje cell dendrites did not differ between the Chase ABC (K)- and CS-A (L)-added conditions. Scale bar, 3 µm. M, Quantitative representation of the effects of Chase ABC, CS, and PTN on the morphogenesis of Purkinje cell dendrites in slice cultures at 6 DIV. n = 3 (CS chains) or 4 (Control, Chase ABC, PTN). Error bars represent SEM. *p < 0.05, **p < 0.005 versus control.
Next we examined the effects of exogenously added CS chains. We indicated previously that various CS samples differentially inhibit the signaling of the PTN-PTP
In our slice culture system, exogenously applied PTN also induced an abnormal morphology in Purkinje cell dendrites (SPD/MPD/DOPD = 37.4:55.2:7.4%) (Fig. 4I,J,M). This may be caused by perturbation of normal distribution of the endogenous PTN by the exogenous PTN.
The morphological change of Purkinje cells from the MPD to the SPD type is accompanied by the formation of many dendritic spines in vivo. This later aspect of maturation appeared not to be influenced by treatment with the reagents affecting PTN-PTP
In contrast to the dendrite formation of Purkinje cells, development of granule cells proceeded normally even in the presence of the reagents affecting PTN-PTP
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Figure 5. Development of granule cells in slice cultures under control and CS-D-added conditions. Cerebellar slices cultured for 6 d without (A,C,E) or with (B,D,F) CS-D were processed for several histological analyses. A, B, Nissl staining with toluidine blue. Migration of granule cells from the EGL to the IGL was nearly completed even in the CS-D-treated cultures. Scale bar, 50 µm. C, D, Confocal microscopic images of cryosections double stained by fluorescent immunohistochemistry using antibodies against NeuN (Cy2, green) and IP3R (Cy3, red). The density of granule cells in the IGL was not significantly different between these two conditions (Table 2). Scale bar, 25 µm. E, F, Cryosections stained by immunohistochemistry using an antibody against vesicular glutamate transporter 1 (VGLUT1). VGLUT1 was expressed in the ML under both conditions. Scale bar, 50 µm.
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Table 2. Evaluation of the density of granule cells Interestingly, Chase ABC digestion of the cerebellar sections markedly reduced the PTN immunoreactivity in the ML (Fig. 6A,B), indicating that most of the endogenous PTN is present in a CS-bound form in this tissue. This also suggests that the effects of Chase ABC and CS chains on the morphogenesis of Purkinje cell dendrites were caused by the displacement of PTN from the ML. In fact, Western blotting showed that the addition of CS-D but not CS-A into the culture medium markedly decreased the PTN contents in the cerebellar slices [control/CS-D/CS-A = 100; 68 ± 8 (p < 0.01 vs control; t test); 100 ± 4% (n = 3)] (Fig. 6C).
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Figure 6. Effects of the Chase ABC and CS treatments on PTN contents in the cerebellum. A, B, Confocal microscopic images of adjacent cryosections derived from the cerebellum of a P9 rat and stained by fluorescent immunohistochemistry using an antibody against PTN without (A) or with (B) pretreatment by Chase ABC (20 mU/ml; 37°C; 40 min). The pretreatment with Chase ABC reduced PTN immunoreactivity. Scale bar, 25 µm. C, Western blotting analysis showing effects of CS-D and -A on PTN contents in cerebellar slice cultures. Addition of CS-D but not CS-A decreased the PTN contents in the slices.
Involvement of GLAST on Bergmann glial processes
Because the GLAST-positive lamellate processes of Bergmann glia expressed PTP
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Figure 7. Reduction in GLAST immunoreactivity on Bergmann glial processes by the reagents affecting PTN-PTP
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Table 3. Evaluation of the number of Bergmann fibers The reduction in GLAST immunoreactivity by the reagents affecting PTN-PTP
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Figure 8. Effects of a glutamate transporter inhibitor on the morphogenesis of Purkinje cell dendrites. A, B, Confocal microscopic images of cerebellar slices derived from P9 rats, cultured for 6 d with culture medium containing DL-threo-
Discussion
The postnatal development of Purkinje cells is characterized by a specific pattern of dendritic morphogenesis. The change of Purkinje cells from the MPD or DOPD type to the SPD type strictly proceeds under in vivo conditions, and almost all of the Purkinje cells are of the SPD type in the matured cerebellum. In our organotypic slice culture system of postnatal rat cerebellum, the morphological changes of Purkinje cells basically proceeded as in vivo (Fig. 1). This suggested that some of the primary dendrites were withdrawn in slice cultures as in vivo. However, more MPD-type Purkinje cells were found in slice cultures at 6 DIV than in P15 cerebellum. In addition, a significant population of Purkinje cells was of the DOPD type at 6 DIV, whereas at the corresponding in vivo stage (P15), this type of Purkinje cell was not observed. We consider that this insufficient progress of Purkinje cell development in slice cultures is caused by a decrease in signal transduction levels required for the dendrite formation under the culture conditions. However, it seems that this property of the slice culture system makes it a highly sensitive assay system for Purkinje cell development. Using this culture system, we demonstrated that the perturbation of PTN-PTP
CS proteoglycans are reported to contribute to the regulation of directed axonal outgrowth of various neurons, including retinal ganglion cells (Brittis and Silver, 1994
The treatment with Chase ABC and CS chains induced an aberrant Purkinje cell morphogenesis in slice cultures (Fig. 4). The same treatments also markedly decreased PTN contents in the cerebellum (Fig. 6), indicating that most PTN is present in the CS proteoglycan-bound form in this tissue. It is notable that the effects of CS chains were highly dependent on the structure of CS chains. Although CS-C, -D, and -E influenced the morphogenesis of Purkinje cells, CS-A gave no effect on this type of cells. CS-C and -D contain ~10-20% GlcUA(2-sulfate)
Although PTP
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Figure 9. A model for regulation of the morphogenesis of Purkinje cell dendrites by PTN-PTP
Our study showed that the immunoreactivity to the glutamate transporter GLAST on the lamellate processes of Bergmann glia was reduced in slice cultures treated with the reagents affecting PTN-PTP
In the developing cerebellum, glutamate is produced and released by granule cells (Levi et al., 1991
In this context, Bergmann glia settle in a quite important position. The cell bodies of Bergmann glia closely associate with Purkinje cell bodies and extend polarized shaft processes with fine lamellate processes toward the pial surface. Of the two, the latter processes express GLAST and closely surround both the cell bodies and dendrites of Purkinje cells during postnatal development (Furuta et al., 1997
Although the directed growth of Purkinje cell dendrites might be regulated simply by the interaction between the leading processes of the dendrites and the Bergmann glial processes (Yamada et al., 2000
-2 voltage-dependent calcium channel accessory subunit was found to increase the MPD-type Purkinje cells (Brodbeck et al., 2002
It was reported recently that mutant mice deficient in PTP
FOOTNOTES Received Aug. 16, 2002; revised Dec. 31, 2002; accepted Jan. 3, 2003.
This study was supported in part by grants-in-aid for scientific research from Fujita Health University and from the Ministry of Education, Science, Sports and Culture of Japan.
Correspondence should be addressed to Masahiko Tanaka, Division of Cell Biology, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan. E-mail: mtanaka{at}fujita-hu.ac.jp.
References
- Altman J, Anderson WJ (1972) Experimental reorganization of the cerebellar cortex. I. Morphological effects of eliminating all microneurons with prolonged X-irradiation started at birth. J Comp Neurol 146:355-406[Web of Science][Medline].
- Amet LEA, Lauri SE, Hienola A, Croll SD, Lu Y, Levorse JM, Prabhakaran B, Taira T, Rauvala H, Vogt TF (2001) Enhanced hippocampal long-term potentiation in mice lacking heparin-binding growth-associated molecule. Mol Cell Neurosci 17:1014-1024[Web of Science][Medline].
- Armengol J-A, Sotelo C (1991) Early dendritic development of Purkinje cells in the rat cerebellum. A light and electron microscopic study using axonal tracing in "in vitro" slices. Dev Brain Res 64:95-114[Medline].
- Bandtlow CE, Zimmermann DR (2000) Proteoglycans in the developing brain: new conceptual insights for old proteins. Physiol Rev 80:1267-1290
[Abstract/Free Full Text] .- Baptista CA, Hatten ME, Blazeski R, Mason CA (1994) Cell-cell interactions influence survival and differentiation of purified Purkinje cells in vitro. Neuron 12:243-260[Web of Science][Medline].
- Barbour B, Keller BU, Llano I, Marty A (1994) Prolonged presence of glutamate during excitatory synaptic transmission to cerebellar Purkinje cells. Neuron 12:1331-1343[Web of Science][Medline].
- Bellocchio EE, Hu H, Pohorille A, Chan J, Pickel VM, Edwards RH (1998) The localization of the brain-specific inorganic phosphate transporter suggests a specific presynaptic role in glutamatergic transmission. J Neurosci 18:8648-8659
[Abstract/Free Full Text] .- Bernhardt RR, Schachner M (2000) Chondroitin sulfates affect the formation of the segmental motor nerve in zebrafish embryo. Dev Biol 221:206-219[Web of Science][Medline].
- Berry M, Bradley P (1976) The growth of the dendritic trees of Purkinje cells in the cerebellum of the rat. Brain Res 112:1-35[Web of Science][Medline].
- Berry M, Bradley P, Borges S (1978) Environmental and genetic determinants of connectivity in the central nervous system
an approach through dendritic field analysis. Prog Brain Res 48:133-146[Medline].
- Brittis PA, Silver J (1994) Exogenous glycosaminoglycans induce complete inversion of retinal ganglion cell bodies and their axons within the retinal neuroepithelium. Proc Natl Acad Sci USA 91:7539-7542
[Abstract/Free Full Text] .- Brodbeck J, Davies A, Courtney J-M, Meir A, Balaguero N, Canti C, Moss FJ, Page KM, Pratt WS, Hunt SP, Barclay J, Rees M, Dolphin AC (2002) The ducky mutation in Cacna2d2 results in altered Purkinje cell morphology and is associated with the expression of a truncated
[Abstract/Free Full Text] .- Canoll PD, Barnea G, Levy JB, Sap J, Ehrlich M, Silvennoinen O, Schlessinger J, Musacchio JM (1993) The expression of a novel receptor-type tyrosine phosphatase suggests a role in morphogenesis and plasticity of the nervous system. Dev Brain Res 75:293-298[Medline].
- Chung KY, Taylor JSH, Shum DKY, Chan SO (2000) Axon routing at the optic chiasm after enzymatic removal of chondroitin sulfate in mouse embryo. Development 127:2673-2683[Abstract].
- Cohen-Cory S, Dreyfus CF, Black IB (1991) NGF and excitatory neurotransmitters regulate survival and morphogenesis of cultured cerebellar Purkinje cells. J Neurosci 11:462-471[Abstract].
- Freshney RI (1987) Three-dimensional culture systems. In: Culture of animal cells: a manual of basic technique, Ed 2, pp 297-307 New York: Alan R. Liss.
- Furuta A, Rothstein JD, Martin LJ (1997) Glutamate transporter protein subtypes are expressed differentially during rat CNS development. J Neurosci 17:8363-8375
[Abstract/Free Full Text] .- Harroch S, Palmeri M, Rosenbluth J, Custer A, Okigaki M, Shrager P, Blum M, Buxbaum JD, Schlessinger J (2000) No obvious abnormality in mice deficient in receptor protein tyrosine phosphatase
[Abstract/Free Full Text] .- Hendelman WJ, Aggerwal AS (1980) The Purkinje neuron: I. A Golgi study of its development in the mouse and in culture. J Comp Neurol 193:1063-1079[Medline].
- Hirai H, Launey T (2000) The regulatory connection between the activity of granule cell NMDA receptors and dendritic differentiation of cerebellar Purkinje cells. J Neurosci 20:5217-5224
[Abstract/Free Full Text] .- Lehre KP, Levy LM, Ottersen OP, Storm-Mathisen J, Danbolt NC (1995) Differential expression of two glial glutamate transporters in the rat brain: quantitative and immunocytochemical observations. J Neurosci 15:1835-1853[Abstract].
- Levi G, Patrizio M, Gallo V (1991) Release of endogenous and newly synthesized glutamate and of other amino acids induced by non-N-methyl-D-aspartate receptor activation in cerebellar granule cell cultures. J Neurochem 56:199-206[Web of Science][Medline].
- Maeda N, Noda M (1998) Involvement of receptor-like protein tyrosine phosphatase
[Abstract/Free Full Text] .- Maeda N, Niinobe M, Inoue Y, Mikoshiba K (1989) Developmental expression and intracellular localization of P400 protein characteristic of Purkinje cells in the mouse cerebellum. Dev Biol 133:67-76[Web of Science][Medline].
- Maeda N, Matsui F, Oohira A (1992) A chondroitin sulfate proteoglycan that is developmentally regulated in the cerebellar mossy fiber system. Dev Biol 151:564-574[Web of Science][Medline].
- Maeda N, Nishiwaki T, Shintani T, Hamanaka H, Noda M (1996) 6B4 proteoglycan/phosphacan, an extracellular variant of receptor-like protein-tyrosine phosphatase
[Abstract/Free Full Text] .- Maeda N, Ichihara-Tanaka K, Kimura T, Kadomatsu K, Muramatsu T, Noda M (1999) A receptor-like protein-tyrosine phosphatase PTP
[Abstract/Free Full Text] .- Matsumoto K, Wanaka A, Mori T, Taguchi A, Ishi N, Muramatsu H, Muramatsu T, Tohyama M (1994) Localization of pleiotrophin and midkine in the postnatal developing cerebellum. Neurosci Lett 178:216-220[Medline].
- Maurel P, Rauch U, Flad M, Margolis RK, Margolis RU (1994) Phosphacan, a chondroitin sulfate proteoglycan of brain that interacts with neurons and neural cell-adhesion molecules, is an extracellular variant of a receptor-type protein tyrosine phosphatase. Proc Natl Acad Sci USA 91:2512-2516
[Abstract/Free Full Text] .- Miranda-Contreras L, Benítez-Diaz PR, Mendoza-Briceño RV, Delgado-Saez MC, Palacios-Prü EL (1999) Levels of amino acid neurotransmitters during mouse cerebellar neurogenesis and in histotypic cerebellar cultures. Dev Neurosci 21:147-158[Medline].
- Nishiwaki T, Maeda N, Noda M (1998) Characterization and developmental regulation of proteoglycan-type protein tyrosine phosphatase
[Abstract/Free Full Text] .- Peles E, Schlessinger J, Grumet M (1998) Multi-ligand interactions with receptor-like protein tyrosine phosphatase
- Qi M, Ikematsu S, Maeda N, Ichihara-Tanaka K, Sakuma S, Noda M, Muramatsu T, Kadomatsu K (2001) Haptotactic migration induced by midkine. Involvement of protein-tyrosine phosphatase
[Abstract/Free Full Text] .- Rakic P, Sidman RL (1973) Organization of cerebellar cortex secondary to deficit of granule cells in weaver mutant mice. J Comp Neurol 152:133-162[Web of Science][Medline].
- Rothstein JD, Martin L, Levey AI, Dykes-Hoberg M, Jin L, Wu D, Nash N, Kuncl RW (1994) Localization of neuronal and glial glutamate transporters. Neuron 13:713-725[Web of Science][Medline].
- Sakai T, Kyogashima M, Kariya Y, Urano T, Takada Y, Takada A (2000) Importance of GlucUA
- Schwartz PM, Borghesani PR, Levy RL, Pomeroy SL, Segal RA (1997) Abnormal cerebellar development and foliation in BDNF
/
- Shimamoto K, LeBrun B, Yasuda-Kamatani Y, Sakaitani M, Shigeri Y, Yumoto N, Nakajima T (1998) DL-threo-
[Abstract/Free Full Text] .- Shintani T, Watanabe E, Maeda N, Noda M (1998) Neurons as well as astrocytes express proteoglycan-type protein tyrosine phosphatase
- Snyder SE, Li J, Schauwecker PE, McNeill TH, Salton SRJ (1996) Comparison of RPTP
- Sotelo C (1975) Anatomical, physiological and biochemical studies of the cerebellum from mutant mice. II. Morphological study of cerebellar cortical neurons and circuits in the weaver mouse. Brain Res 94:19-44[Web of Science][Medline].
- Stoppini L, Buchs P, Muller D (1991) A simple method for organotypic cultures of nervous tissue. J Neurosci Methods 37:173-182[Web of Science][Medline].
- Tanaka M, Tomita A, Yoshida S, Yano M, Shimizu H (1994) Observation of the highly organized development of granule cells in rat cerebellar organotypic cultures. Brain Res 641:319-327[Web of Science][Medline].
- Ullensvang K, Lehre KP, Storm-Mathisen J, Danbolt NC (1997) Differential developmental expression of the two rat brain glutamate transporter proteins GLAST and GLT. Eur J Neurosci 9:1646-1655[Web of Science][Medline].
- Watase K, Hashimoto K, Kano M, Yamada K, Watanabe M, Inoue Y, Okuyama S, Sakagawa T, Ogawa S, Kawashima N, Hori S, Takimoto M, Wada K, Tanaka K (1998) Motor discoordination and increased susceptibility to cerebellar injury in GLAST mutant mice. Eur J Neurosci 10:976-988[Web of Science][Medline].
- Wewetzer K, Rauvala H, Unsicker K (1995) Immunocytochemical localization of the heparin-binding growth-associated molecule (HB-GAM) in the developing and adult rat cerebellar cortex. Brain Res 693:31-38[Medline].
- Wilson MT, Keith CH (1998) Glutamate modulation of dendrite outgrowth: alterations in the distribution of dendritic microtubles. J Neurosci Res 52:599-611[Medline].
- Yamada K, Fukaya M, Shibata T, Kurihara H, Tanaka K, Inoue Y, Watanabe M (2000) Dynamic transformation of Bergmann glial fibers proceeds in correlation with dendritic outgrowth and synapse formation of cerebellar Purkinje cells. J Comp Neurol 418:106-120[Web of Science][Medline].
- Yamamoto N, Kurotani T, Toyama K (1989) Neural connections between the lateral geniculate nucleus and visual cortex in vitro. Science 245:192-194
[Abstract/Free Full Text] .
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A. Purushothaman, J. Fukuda, S. Mizumoto, G. B. ten Dam, T. H. van Kuppevelt, H. Kitagawa, T. Mikami, and K. Sugahara
Functions of Chondroitin Sulfate/Dermatan Sulfate Chains in Brain Development: CRITICAL ROLES OF E AND iE DISACCHARIDE UNITS RECOGNIZED BY A SINGLE CHAIN ANTIBODY GD3G7
J. Biol. Chem., July 6, 2007; 282(27): 19442 - 19452.
[Abstract] [Full Text] [PDF]
C. M. Galtrey, R. A. Asher, F. Nothias, and J. W. Fawcett
Promoting plasticity in the spinal cord with chondroitinase improves functional recovery after peripheral nerve repair
Brain, April 1, 2007; 130(4): 926 - 939.
[Abstract] [Full Text] [PDF]
R. Mi, W. Chen, and A. Hoke
From the Cover: Pleiotrophin is a neurotrophic factor for spinal motor neurons
PNAS, March 13, 2007; 104(11): 4664 - 4669.
[Abstract] [Full Text] [PDF]
A. Jurewicz, M. Matysiak, C. S. Raine, and K. Selmaj
Soluble Nogo-A, an inhibitor of axonal regeneration, as a biomarker for multiple sclerosis
Neurology, January 23, 2007; 68(4): 283 - 287.
[Abstract] [Full Text] [PDF]
Y.-J. Sun, K. Nishikawa, H. Yuda, Y.-L. Wang, H. Osaka, N. Fukazawa, A. Naito, Y. Kudo, K. Wada, and S. Aoki
Solo/Trio8, a membrane-associated short isoform of trio, modulates endosome dynamics and neurite elongation.
Mol. Cell. Biol., September 1, 2006; 26(18): 6923 - 6935.
[Abstract] [Full Text] [PDF]
C. Mitsunaga, T. Mikami, S. Mizumoto, J. Fukuda, and K. Sugahara
Chondroitin Sulfate/Dermatan Sulfate Hybrid Chains in the Development of Cerebellum: SPATIOTEMPORAL REGULATION OF THE EXPRESSION OF CRITICAL DISULFATED DISACCHARIDES BY SPECIFIC SULFOTRANSFERASES
J. Biol. Chem., July 14, 2006; 281(28): 18942 - 18952.
[Abstract] [Full Text] [PDF]
N. Maeda, N. Fukazawa, and T. Hata
The Binding of Chondroitin Sulfate to Pleiotrophin/Heparin-binding Growth-associated Molecule Is Regulated by Chain Length and Oversulfated Structures
J. Biol. Chem., February 24, 2006; 281(8): 4894 - 4902.
[Abstract] [Full Text] [PDF]
X. Bao, T. Muramatsu, and K. Sugahara
Demonstration of the Pleiotrophin-binding Oligosaccharide Sequences Isolated from Chondroitin Sulfate/Dermatan Sulfate Hybrid Chains of Embryonic Pig Brains
J. Biol. Chem., October 21, 2005; 280(42): 35318 - 35328.
[Abstract] [Full Text] [PDF]
L. Corvetti and F. Rossi
Degradation of Chondroitin Sulfate Proteoglycans Induces Sprouting of Intact Purkinje Axons in the Cerebellum of the Adult Rat
J. Neurosci., August 3, 2005; 25(31): 7150 - 7158.
[Abstract] [Full Text] [PDF]
X. Bao, M. S. G. Pavao, J. C. dos Santos, and K. Sugahara
A Functional Dermatan Sulfate Epitope Containing Iduronate(2-O-sulfate){alpha}1-3GalNAc(6-O-sulfate) Disaccharide in the Mouse Brain: DEMONSTRATION USING A NOVEL MONOCLONAL ANTIBODY RAISED AGAINST DERMATAN SULFATE OF ASCIDIAN ASCIDIA NIGRA
J. Biol. Chem., June 17, 2005; 280(24): 23184 - 23193.
[Abstract] [Full Text] [PDF]
Y. Ito, M. Hikino, Y. Yajima, T. Mikami, S. Sirko, A. von Holst, A. Faissner, S. Fukui, and K. Sugahara
Structural characterization of the epitopes of the monoclonal antibodies 473HD, CS-56, and MO-225 specific for chondroitin sulfate D-type using the oligosaccharide library
Glycobiology, June 1, 2005; 15(6): 593 - 603.
[Abstract] [Full Text] [PDF]
G. Lorente, A. Nelson, S. Mueller, J. Kuo, R. Urfer, K. Nikolich, and E. D. Foehr
Functional comparison of long and short splice forms of RPTP{beta}: Implications for glioblastoma treatment
Neuro-oncol, April 1, 2005; 7(2): 154 - 163.
[Abstract] [PDF]
X. Bao, S. Nishimura, T. Mikami, S. Yamada, N. Itoh, and K. Sugahara
Chondroitin Sulfate/Dermatan Sulfate Hybrid Chains from Embryonic Pig Brain, Which Contain a Higher Proportion of L-Iduronic Acid than Those from Adult Pig Brain, Exhibit Neuritogenic and Growth Factor Binding Activities
J. Biol. Chem., March 12, 2004; 279(11): 9765 - 9776.
[Abstract] [Full Text] [PDF]
M. B. Genter, P. P. Van Veldhoven, A. G. Jegga, B. Sakthivel, S. Kong, K. Stanley, D. P. Witte, C. L. Ebert, and B. J. Aronow
Microarray-based discovery of highly expressed olfactory mucosal genes: potential roles in the various functions of the olfactory system
Physiol Genomics, December 16, 2003; 16(1): 67 - 81.
[Abstract] [Full Text] [PDF]
N. Maeda, J. He, Y. Yajima, T. Mikami, K. Sugahara, and T. Yabe
Heterogeneity of the Chondroitin Sulfate Portion of Phosphacan/6B4 Proteoglycan Regulates Its Binding Affinity for Pleiotrophin/Heparin Binding Growth-associated Molecule
J. Biol. Chem., September 12, 2003; 278(37): 35805 - 35811.
[Abstract] [Full Text] [PDF]
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