Developmental change and function of chondroitin sulfate deposited around cerebellar Purkinje cells.
Chondroitin sulfate is a long sulfated polysaccharide with enormous structural heterogeneity that binds with various proteins, such as growth factors, in a structure-dependent manner. In this study, we analyzed the expression of chondroitin sulfate in the postnatally developing cerebellar cortex by using three monoclonal antibodies against chondroitin sulfate, MO-225, 2H6, and CS-56, which recognize different structural domains in this polysaccharide. During the first postnatal week, the patterns of immunohistochemical staining made by these antibodies were quite similar, and the molecular layer, the granule cell layer, and Bergmann glial fibers in the external granular layer were densely stained. After postnatal day 12 (P12), the expression of 2H6 epitopes was down-regulated in the molecular layer, and the expression of CS-56 epitopes in this layer was also reduced after P16. On the other hand, the strong expression of MO-225 epitopes, GlcA(2S)beta1-3GalNAc(6S) (D unit)-containing structures, remained until adulthood. These chondroitin sulfate epitopes were observed around Purkinje cells, including cell soma and dendrites. Detailed immunohistochemical analysis suggested that chondroitin sulfate was deposited between Purkinje cell surfaces and the processes of Bergmann glia. Furthermore, the amount of pleiotrophin, a heparin-binding growth factor, in the cultured cerebellar slices was remarkably diminished after treatment with chondroitinase ABC or D unit-rich chondroitin sulfate. With the previous findings that pleiotrophin binds to D unit-rich chondroitin sulfate, we suggest that the D-type structure is important for the signaling of pleiotrophin, which plays roles in Purkinje cell-Bergmann glia interaction, and that the structural changes of chondroitin sulfate regulate this signaling pathway.
Shimazaki
Yumiko
Y
Department of Developmental Neuroscience, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan.
Nagata
Isao
I
Ishii
Maki
M
Tanaka
Masahiko
M
Marunouchi
Tohru
T
Hata
Toshihiro
T
Maeda
Nobuaki
N
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000918:Antibody Specificity; D002352:Carrier Proteins / Q000378:metabolism; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology; D002525:Cerebellar Cortex / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D019765:Chondroitin ABC Lyase / Q000494:pharmacology; D002809:Chondroitin Sulfates / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D015536:Down-Regulation / Q000502:physiology; D000939:Epitopes / Q000276:immunology; D005109:Extracellular Matrix / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D009924:Organ Culture Techniques; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011689:Purkinje Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D000911:Antibodies, Monoclonal; D002352:Carrier Proteins; D016207:Cytokines; D000939:Epitopes; C066845:pleiotrophin; D002809:Chondroitin Sulfates; D019765:Chondroitin ABC Lyase