DEFASCICULATION OF NEURITES IS MEDIATED BY TENASCIN-R AND ITS NEURONAL RECEPTOR F3 11/

Fasciculation and defasciculation of axone are major morphogenetic eve nts in the formation of neuronal pathways during development, We have identified the extracellular matrix glycoprotein tenascin-R (TN-R) and its neuronal receptor, the immunoglobulin superfamily recognition mol ecule F3, as promoters of neurite defasciculation in cerebellar explan t cultures, Perturbation of the interaction between these two molecule s using both antibodies and an antisense oligonucleotide resulted in i ncreased neurite fasciculation, The domains involved in defasciculatio n were identified as the N-terminal region of TN-R containing the cyst eine-rich stretch and the 4.5 epidermal growth factor-like repeats and the immunoglobulin-like domains of F3. Fasciculation induced by antib odies and the antisense oligonucleotide could be reverted by a phorbol ester activator of protein kinase C, whereas the protein kinase inhib itor staurosporine increased fasciculation, Our observations indicate that defasciculated neurite outgrowth does not only depend on the redu ction of the expression of fasciculation enhancing adhesion molecules, such as L1 and the neural cell adhesion molecule (NCAM), but also on recognition molecules that actively induce defasciculation by triggeri ng second messenger systems. (C) 1998 Wiley-Liss, Inc.