Sympathetic innervation-mediating protein.

The present study was performed to elucidate the mechanisms and molecular basis of specific innervation of the peripheral tissues. Chick sympathetic nerve fibers densely innervate expansor secundariorum muscle, but not skeletal muscle. When a sympathetic ganglion was cultured in collagen gel with muscle explants, the ganglion extended neurites towards two types of muscles to the same extent. Dissociated sympathetic ganglion neurons adhered firmly to the dish precoated with materials from expansor secundariorum but not to the dish precoated with those from skeletal muscle. Sympathetic nerve fibers were found densely distributed on the substrate from expansor secundariorum but not on the substrate from skeletal muscle. These results suggest that neuronal recognition mechanisms are involved in the process of selective sympathetic innervation of the expansor secundariorum muscle of the chick. The protein which caused the dense distribution of sympathetic fibers as the substrate has been purified from heart-cell-conditioned medium. The most purified fraction showed a single band with an apparent molecular weight of 370,000 daltons on SDS-PAGE under non-reducing and reducing conditions. The biological activity of the protein was over 100 times higher than that of laminin. Antiserum was raised against the factor in heart-cell-conditioned medium that induced the dense distribution of sympathetic fibers in culture. Addition of the antiserum to the culture medium inhibited the dense distribution of sympathetic fibers on the purified protein-substrate without affecting the general growth of the fibers. Subcutaneous injection of the antiserum into the chicks inhibited the regeneration of adrenergic fibers following 6-hydroxydopamine-induced axotomy in peripheral tissues (heart, spleen, kidney and blood vessel).(ABSTRACT TRUNCATED AT 250 WORDS)