DEVELOPMENTAL AND FGF-2-MEDIATED REGULATION OF SYNDECANS(1-4) AND GLYPICAN IN OLIGODENDROCYTES

Differentiating cells undergo developmentally regulated changes in cel l-cell and cell-matrix adhesion that control migration through microen vironments, proliferation, and differentiation. The diversity of the p atterns of expression of heparan sulfate proteoglycans (HSPGs), couple d with their interactions with extracellular matrix, cell adhesion mol ecules, and growth factors, has emphasized their critical importance i n the regulation of these events. Syndecans (1-4), glypican, and cereb roglycan are membrane-associated HSPGs that have been implicated in th ese events in various tissues and several tumor cell lines. We have ex amined the developmental expression and FGF-2-mediated regulation of t hese HSPGs during differentiation within a specific lineage of primary cells, oligodendrocytes (OL). Northern analyses of highly purified, d evelopmentally synchronized populations of OL-lineage cells at three s tages of differentiation (early and late progenitors and mature OLs) s howed that the expression of individual forms of these syndecans and g lypican are developmentally regulated. Specifically, the level of expr ession of syndecan-2 and -4 and glypican mRNAs increased as the cells differentiated from proliferative late progenitors to post-mitotic mat ure cells. The expression of syndecan-1 and -3 had the inverse develop mental pattern. Therefore, these two sets of molecules may have differ ent roles in regulating the onset of terminal differentiation in OLs. The levels of mRNA expression were regulated by FGF-2: in late progeni tors, FGF-2 induced a doubling of the mRNA levels of syndecan-2, -3, a nd -4, while those for syndecan-1 and glypican remained unaffected; in mature OLs, the levels of syndecan-1 mRNA were up-regulated, the leve ls of syndecan-2 and -4 and glypican were down-regulated. These result s suggest that the individual syndecan molecules have distinct functio ns during the differentiation process and that multiple levels of regu lation must exist, leading to a changing repertoire of these molecules during OL lineage progression and myelinogenesis.