INFLUENCE OF JANUSIN AND TENASCIN ON GROWTH CONE BEHAVIOR IN-VITRO

Janusin and tenascin are glia-derived, structurally related, extracell ular matrix glycoproteins of the J1 family that are expressed in vivo at times and in locations where active neurite outgrowth occurs, but a lso when the formation or stabilization of cytoarchitectonic boundarie s appears to be in operation. To resolve this apparent functional dich otomy, we have studied the behavioral response of growth cones, growin g in culture on the permissive substrate laminin, to janusin and tenas cin, by video time lapse microscopy. When janusin and tenascin were of fered as sharp substrate boundaries, dorsal root ganglion (DRG) and re tinal ganglion neuron growth cones avoided growing on these molecules, but were not induced to collapse. On the other hand, when janusin and tenascin were offered, in a mixture with laminin, as uniform substrat es, DRG growth cones displayed a collapsed morphology and were able to advance at a faster rate than on laminin alone. In contrast, the outg rowth of retinal ganglion neuron growth cones was completely inhibited under these conditions, underscoring a cell type specificity in the r esponse of growth cones to these molecules. Using several monoclonal a ntibodies binding to distinct epitopes on the tenascin molecule, we ha ve identified two domains responsible for growth cone repulsion, on ep idermal growth factor (EGF)-like repeats 3-5 and fibronectin type III homologous repeats 4 and 5. These domains are different from the one p reviously recognized to be involved in neurite outgrowth on a uniform tenascin substrate. We conclude that both molecules may promote or ret ard growth cone advance, depending on the spatial expression pattern a nd the neuronal cell type.