3 FORMS OF RPTP-BETA ARE DIFFERENTIALLY EXPRESSED DURING GLIOGENESIS IN THE DEVELOPING RAT-BRAIN AND DURING GLIAL-CELL DIFFERENTIATION IN CULTURE

In situ hybridization and Northern analysis demonstrate that the three splicing variants of RPTP-beta have different spatial and temporal pa tterns of expression in the developing brain, The 9.5-kb and 6.4-kb tr anscripts, which encode transmembrane protein tyrosine phosphatases wi th different extracellular domains, are predominantly expressed in gli al progenitors located in the subventricular zone (SVZ). The 8.4-kb tr anscript, which encodes a secreted chondroitin sulfate proteoglycan (p hosphacan), is expressed at high levels by more mature glia that have migrated out of the SVZ, The three transcripts are also differentially expressed in glial cell cultures; O2A progenitors express high levels of the 9.5- and 8.4-kb transcript, whereas type 1 astrocyte progenito rs predominantly express the 6.4-kb transcript, C6 gliomas also expres s high levels of the 6.4-kb transcript, Treating C6 cells with the dif ferentiating agent dibutyryl cyclic-AMP (DBcAMP), induces a decrease i n the 6.4-kb transcript and a corresponding increase in the 8.4-kb tra nscript, O2A cells grown in the presence of basic fibroblast growth fa ctor (bFGF) and platelet-derived growth factor (PDGF) remain highly pr oliferative and undifferentiated, and continue to express high levels of RPTP-beta. However, when O2A cells are grown in conditions that ind uce oligodendrocyte differentiation, there is a marked decrease in the expression of the transmembrane forms of RPTP-beta, as determined by immunofluorescence. These results demonstrate that RPTP-beta expressio n is regulated during glial cell differentiation and suggest that the different forms of RPTP-beta perform distinct functions during brain d evelopment, (C) 1996 Wiley-Liss, Inc.