IS LAMININ-1 A GUIDANCE CUE FOR CEREBELLAR GRANULE CELL-MIGRATION

Laminin-1 is a glycoprotein found in the basement membrane of many tis sues, In the cerebellum of rodents, it has also been localized along B ergmann glial fibers, where iris thought to be involved in promoting g ranule cell migration by enhancing adhesion and neurite outgrowth alon g these fibers, Recent reports, however, indicate that laminin-l is no t present on Bergmann fibers, but instead is associated with blood ves sels and meninges, Furthermore, attempts to block granule cell migrati on using antibodies against laminin-l have yielded conflicting results , In this report, we provide further evidence that laminin-l is associ ated exclusively with blued vessels and meninges in the cerebellum of postnatal rats, In addition, me show that adhesion and neurite outgrow th of granule cells was impeded on laminin-coated surfaces, In fact, c erebellar cells dramatically and consistently avoided laminin-1 region s of patterned surfaces, Cells did adhere to laminin regions if it was coadsorbed with polylysine or tested in serum-containing medium. Avoi dance of laminin-1 regions in culture was not, however, blocked by pre treatment with laminin-l antibodies, By comparison, mouse neuroblastom a cells adhered preferentially to laminin-1 regions in serum-free medi um, a response which was blocked by laminin-l antibodies, These result s indicate that laminin-l is not involved in granule cell migration al ong Bergmann glial fibers, Instead, they suggest that laminin-1 may fu nction as a repulsive guidance cue preventing granule cells from follo wing inappropriate pathways during development. (C) 1997 John Wiley & Sons, Inc.