BETA(1) INTEGRINS REGULATE AXON OUTGROWTH AND GLIAL-CELL SPREADING ONA GLIAL-DERIVED EXTRACELLULAR-MATRIX DURING DEVELOPMENT AND REGENERATION

In the present study we have investigated functional roles for beta(1) inte,orin receptors in regulating axon outgrowth, and glial cell adhe sion and spreading in the Xenopus retina. The XR1 glial cell line, iso lated from Xenopus retinal neuroepithelium, deposits a proteinaceous e xtracellular matrix (ECM) with potent neurite outgrowth promoting acti vity. To investigate a potential role of the integrins as cellular rec eptors for these glial cell-derived ECM components, embryonic and rege nerating retinal explants were cultured in the presence of polyclonal antibodies directed against the beta(1), integrin receptor complex. Th e IgGs and Fabs of the anti-beta(1) integrin antibody strongly inhibit ed ganglion cell axon outgrowth on the glial cell-derived ECM, althoug h axons grew freely across the surfaces of glial cells surrounding the explants. The antibodies also inhibited outgrowth on purified laminin containing substrates in a dose-dependent fashion. In addition, the a nti-beta(1) antibodies were effective at inhibiting the spreading of g lial cells that migrated out from the embryonic explants, and also inh ibited attachment and spreading of Xenopus XR1 glial cells on ECM subs trates. These results show that the beta(1) integrins play important f unctional roles in axon outgrowth during development and regeneration, and also serve in regulating retinal glial cell attachment and spread ing in vitro, and thus are likely to play similar roles in vivo.