TENASCIN-C IN PERIPHERAL-NERVE MORPHOGENESIS

The extracellular matrix (ECM) molecule tenascin/cytotactin (TN-C) is expressed at a high level by satellite (glial precursor) cells in deve loping peripheral nerves of the chick embryo; synthesis of its mRNA pe aks at the time period when axonal growth is maximal. When offered as a substrate in vitro, TN-C mediates neurite outgrowth by both motor an d sensory neurons. The ability to grow neurites on TN-C is development ally regulated: sensory neurons from 4-day-old chick embryos (the stag e at which peripheral nerves start to develop) grow immediately and ra pidly, whereas neurons from older embryos respond with a long delay. A TN-C domain responsible for this activity is located within the C-ter minal (distal) portion of TN-C subunits. integrin receptors seem to be involved on peripheral neurites because their growth on TN-C is compl etely blocked by antibodies to PI integrins. In striking contrast to n euronal processes, nerve satellite cells can attach to a TN-C substrat e but are completely inhibited in their migratory activity. Artificial substrate borders between tenascin and fibrnoectin or laminin act as selective barriers that allow neurites to pass while holding up satell ite cells. The repulsive action of TN-C on satellite cells is similar to that observed for other cell types and is likely to be mediated by additional TN-C domains. In view of these data, it is surprising that mice seem to develop normally without a functional TN-C gene. TN-C is likely to be redundant, that is, its dual action on cell adhesion is s hared by other molecules. However, this function per se is probably im portant for peripheral nerve development. TN-C or related molecules mi ght set up transient boundaries between nerve fascicles and the mesenc hyme. Such boundaries are respected by satellite cells but still allow neurites to pass and sort out.