Neural precursors express multiple chondroitin sulfate proteoglycans, including the lectican family.
Chondroitin sulfate proteoglycans (CSPGs) abnormally accumulate in cerebrospinal fluid (CSF) of both human neonates with preterm hydrocephalus, and P8 hydrocephalic mice. We hypothesized CSF CSPGs are synthesized by neural precursors, separated from ventricular CSF by ependyma, which is often disrupted in hydrocephalus. Western blotting demonstrates that neural precursors cultured as neurospheres secrete CSPGs (> 30 microg/ml) into their media which appear to be very similar to these CSF CSPGs. Some CSPGs bear the stage-specific embryonic antigen-1 (ssea-1), associated with embryonic/neural stem cells. Neurospheres transcribe many CSPG genes, including the entire aggrecan/lectican family, phosphacan, and tenascin. Phosphacan can be detected in media by Western blotting. Aggrecan can be detected in media after purification using hyaluronic acid affinity chromatography. During differentiation, neurospheres downregulate CSPGs. This is the first report to show that proliferating neural precursors synthesize lecticans, including aggrecan, which are downregulated with differentiation. These observations suggest novel links between CSPGs and CNS precursor biology.
Kabos
Peter
P
Department of Pediatrics, Division of Molecular and Human Genetics, Children's Research Institute, The Ohio State University, Columbus, OH, USA.
Matundan
Harry
H
Zandian
Mandana
M
Bertolotto
Cristina
C
Robinson
Michael L
ML
Davy
Brian E
BE
Yu
John S
JS
Krueger
Richard C
RC
D053674:Aggrecans; D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000648:ultrastructure; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D011508:Chondroitin Sulfate Proteoglycans / Q000096:biosynthesis* / Q000134:cerebrospinal fluid; D003713:Dendritic Cells / Q000378:metabolism / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins; D006849:Hydrocephalus / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D037181:Lectins, C-Type; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D011509:Proteoglycans / Q000096:biosynthesis / Q000134:cerebrospinal fluid; D012313:RNA / Q000096:biosynthesis; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
C508320:Acan protein, mouse; D053674:Aggrecans; D011508:Chondroitin Sulfate Proteoglycans; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans; D012313:RNA; C516895:PTPRZ1 protein, human; C516896:Ptprz1 protein, mouse; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5