tenascin. Immunohistochemistry revealed tenascin in everyone’s favorite extracellular matrix: around motile cells, at hot spots of proliferation and at sites of branching morphogenesis, near inductive events, in cartilage, tendons

In the early 1980s several labs independently discovered and characterized the glycoprotein that eventually became known as tenascin. Immunohistochemistry revealed tenascin in everyone’s favorite extracellular matrix: around motile cells, at hot spots of proliferation and at sites of branching morphogenesis, near inductive events, in cartilage, tendons and quite prominently in the developing nervous system. Tenascin was also shown to be upregulated at the margins of healing wounds and in the stroma of many tumours (for reviews see Erickson, 1993a; Tucker, 1994; ChiquetEhrismann, 1995; Mackie, 1997). The results of in vitro studies were just as titillating. In contrast to most substrateadhesion molecules, purified tenascin has anti-adhesive properties. Most cells can attach weakly to tenascin-coated substrata, but they remain rounded and particularly motile (e.g. Lotz et al., 1989; Halfter et al., 1989). Tenascin was touted as a ‘magic bullet’, potentially responsible for key events in systems as diverse as neural-crest morphogenesis and tumour metastasis. The cloning and sequencing of tenascin eventually revealed a family of molecules in which tenascin’s distinctive EGF-like repeats and fibrinogen-like C terminus are separated by a series of fibronectin type III repeats (Fig. 1; reviewed by ChiquetEhrismann et al., 1994a). The tenascin discovered first was named tenascin-C to distinguish it from tenascin-R, which is found almost exclusively in the central nervous system (CNS), and tenascin-X, a mammalian tenascin found in some connective tissue and around blood vessels. Tenascin-C was cloned from zebrafish, amphibians, birds and mammals, and its highly conserved sequences provided further evidence for its fundamental function (Fig. 1; Chiquet-Ehrismann et al., 1994a; Erickson, 1994). The precise function(s), however, remained elusive. Cell culture studies showed that tenascin-C promotes both adhesion and detachment, and can stimulate and inhibit cell division, and that its ability to bind to classic integrins depends on the species from which the tenascin-C was isolated (for reviews see Erickson, 1993a; Faissner et al., 1994). Some of the differences are probably related to the type of cell under investigation or the bioassay used. It also seemed likely that at least some of the contradictory observations would be explained by studies of the many tenascin-C splice variants (e.g. Mackie and Tucker, 1992). Many of us were shocked to learn that tenascin-C-knockout mice, among the first to be made by homologous recombination, were indistinguishable from their wild-type littermates (Saga et al., 1992): the tenascin-C-knockout mice were the same size as the controls; they were fertile; and cursory histological examinations revealed no gross deficits in neuroarchitecture or principal organ systems (Fig. 2). Not only had gene-knockout technology failed to clarify a function for tenascin-C, it pointed to a minor or even completely redundant role for this protein (Erickson, 1993b). 3847 Journal of Cell Science 112, 3847-3853 (1999) Printed in Great Britain © The Company of Biologists Limited 1999 JCS0725