Influence of janusin and tenascin on growth cone behavior in vitro

Abstract

Janusin and tenascin are glia-derived, structurally related, extracellular matrix glycoproteins of the J1 family that are expressed in vivo at times and in locations where active neurite outgrowth occurs, but also when the formation or stabilization of cytoarchitectonic boundaries appears to be in operation. To resolve this apparent functional dichotomy, we have studied the behavioral response of growth cones, growing in culture on the permissive substrate laminin to janusin and tenascin, by video time lapse microscopy. When janusin and tenascin were offered as sharp substrate boundaries, dorsal root ganglion (DRG) and retinal 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 substrates, DRG growth cones displayed a collapsed morphology and were able to advance at a faster rate than on laminin alone. In contrast, the outgrowth of retinal ganglion neuron growth cones was completely inhibited under these conditions, underscoring a cell type specificity in the response of growth cones to these molecules. Using several monoclonal antibodies binding to distinct epitopes on the tenascin molecule, we have identified two domains responsible for growth cone repulsion, on epidermal growth factor (EGF)-like repeats 3-5 and fibronectin type III homologous repeats 4 and 5. These domains are different from the one previously recognized to be involved in neurite outgrowth on a uniform tenascin substrate. We conclude that both molecules may promote or retard growth cone advance, depending on the spatial expression pattern and the neuronal cell type.

Repellent Guidance of Regenerating Optic Axons by Chondroitin Sulfate Glycosaminoglycans in Zebrafish

“…Soluble CSs promote the growth of optic axons of goldfish (Challacombe and Elam, 1997). This underscores that the axonal reaction to CSs (Snow and Letourneau, 1992;Snow et al, 1996;Hynds and Snow, 1999) and also to other matrix molecules, such as tenascins (Lochter et al, 1991Lochter and Schachner, 1993;Pesheva et al, 1993;Taylor et al, 1993), depends on the way the molecules are presented to the axons (as a homogeneous or step gradient substrate or soluble in the culture medium). The complex reactions of developing optic axons in slice cultures of the optic chiasm of mice (Chung et al, 2000) to the removal of CSs may be related to the potential role of the spatial configuration in which the molecules are encountered in a specific CNS structure.…”

“…However, there are additional molecules that could contribute to the inhibition of axon growth through the border of nonretinorecipient pretectal nuclei and could in part substitute for the function of CSs after chondroitinase treatment. One of these molecules may be tenascin-R, because it also repels optic axons of chicks (Taylor et al, 1993), salamanders (Becker et al, 1999), and mice (T. . In fact, tenascin-R immunoreactivity is stronger in the accessory pretectal nucleus than in the magnocellular superficial/posterior pretectal nucleus, which correlates with the absence of invading fibers in the accessory pretectal nucleus after chondroitinase treatment (data not shown).…”

Tenascin-R Is an Intrinsic Autocrine Factor for Oligodendrocyte Differentiation and Promotes Cell Adhesion by a SulfatideMediated Mechanism

“…The expression of TN-R by OLs and in myelin coincides with the process of myelination, whereafter both mRNA and protein levels are downregulated to lower values in adulthood (Pesheva et al, 1989;Fuss et al, 1993). Mammalian TN-R is adhesive for astrocytes and antiadhesive for various CNS neurons, i.e., it causes the detachment of neuronal cells from and inhibits axonal outgrowth into TN-R-containing substrates in vitro by its interaction with the neuronal protein F3/11 (Pesheva et al, 1989(Pesheva et al, , 1991Morganti et al, 1990;Taylor et al, 1993).…”

Requirement of the hyaluronan receptor RHAMM in neurite extension and motility as demonstrated in primary neurons and neuronal cell lines

“…This complexity is analogous to the multiple domain structure of such ECM proteins as fibronectin (Limper and Roman, 1992) and such cellspecific adhesion molecule as NCAMs (Wallis and Walsh, 1992). Interference with the function of these specific domains or receptor subunits impairs adhesion, growth, and other properties of neurites, depending on the moiety targeted (Carri et al, 1988;Neugebauer et al, 199 1;Doherty et al, 1992;Appel et al, 1993;Taylor et al, 1993). The present results are consistent with a similar existence of multiple RHAMM domains or isoforms that are differentially expressed and that may perform distinct cell-specific functions.…”