Differential outgrowth of retinal neurites on purified extracellular matrix molecules

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Abstract
Organotgpic cultures of the embryonic retina were system. Microexplants from the chick retina (embryonic day 6) were grown in medium matrix molecules adsorbed to plastic at various concentrations. The maximum neurite length obtained on each type of substratum was measured on day 4 of vitronectin or a hyaluronate‐binding chondroitin sulmolecules On neurite during containing appropriate trophic On purified fate proteoglycan. In contrast, neurite was strongly promoted on laminin in a dose‐dependent manner. Fibronectin elicited a neurite outgrowth corresponding to about one‐third the length Of the Outgrowth On laminin. A 319000‐dalton fibronectin moted by the intact fibronectin molecule. Other isolated domains Of fibronectin, including the 1059000‐ dalton “cell‐binding” domain, did not allow neurite outgrowth. Furthermore, preincubation of fibronec tin substratum with antibodies to the heparin‐binding to fragment elicited neurite elongation the heParin‐binding fibronectin fragment entirely Prevented outgrowth. Fiber Outgrowth was evoked On substrata Of Platelet factor 4, a protein binding heparan Adding increasing concentrations of heparin Progressively inhibited the neurite extension on laminin, whereas similar addition of soluble chondroitin sulfate Proteogbcan had no effect. The results indicate that growing retinal neurites show strong preference for indicate that laminin versus fibronectin. Moreover, the outgrowth‐ to be localized to their heparin‐binding regions. It is tern, elongating retinal neurites can actively discriminate between different extracellular molecules by a mechanism that may involve participation of cell surface heparan sulfate proteoglycans.