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The Journal of Neuroscience, August 1, 2002, 22(15):6596-6609

Tenascin-C Promotes Neurite Outgrowth of Embryonic Hippocampal Neurons through the Alternatively Spliced Fibronectin Type III BD Domains via Activation of the Cell Adhesion Molecule F3/Contactin

Franck Rigato¹, Jeremy Garwood¹, Valérie Calco¹, Nicolas Heck¹, Catherine Faivre-Sarrailh², and Andreas Faissner³

¹ Laboratoire de Neurobiologie du Développement et de la Régénération, Centre National de la Recherche Scientifique, Formation der Recherche en Évolution 2373, F-67084 Strasbourg, France, ² Laboratoire de Génétique et de Physiologie de Développement, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 6545, F-13288 Marseille, France, and ³ Department of Cell Morphology and Molecular Neurobiology, Ruhr-University, 44801 Bochum, Germany

Tenascin-C is a multimodular glycoprotein that possesses neurite outgrowth-stimulating properties, and one functional site has been localized to the alternatively spliced fibronectin type III domain D. To identify the neuronal receptor that mediates this effect, neighboring pairs of fibronectin type III domains were expressed as hybrid proteins fused to the Fc fragment of human immunoglobulin. These IgFc fusions were tested for neurite outgrowth-promoting properties on embryonic day 18 rat hippocampal neurons, and both the combinations BD and D6 were shown to promote the elongation of the longest process, the prospective axon. Antibodies to the cell adhesion molecule F3/contactin of the Ig superfamily blocked the BD- but not the D6-dependent effect. Biochemical studies using F3/contactin-IgFc chimeric proteins confirmed that the adhesion molecule selectively reacts with the combination BD but not with other pairs of fibronectin type III repeats of tenascin-C. The alternatively spliced BD cassettes are prominently expressed in the developing hippocampus, as shown by reverse transcription PCR, and colocalize with F3 expression during perinatal periods when axon growth and the establishment of hippocampal connections take place. We conclude that F3/contactin regulates axon growth of hippocampal neurons in response to tenascin-C.

Key words: tenascin-C; F3/contactin/F11; extracellular matrix; cell adhesion molecules; neurite outgrowth; hippocampus development

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22156596-14$05.00/0

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