SPATIALLY RESTRICTED INCREASE IN POLYSIALIC ACID ENHANCES CORTICOSPINAL AXON BRANCHING RELATED TO TARGET RECOGNITION AND INNERVATION

The polysialic acid (PSA) modification of the neural cell adhesion mol ecule (NCAM) has been shown to alter the responses of developing axons to their environment. We have studied the potential role of PSA in re gulating the innervation of the spinal cord by corticospinal axons, wh ich occurs by a delayed formation of collateral branches from the pare nt axons. Developmental changes in the distribution of PSA were examin ed immunohistochemically using light and electron microscopy, Whereas NCAM is distributed along the entire pathway of rat corticospinal axon s as they grow from the cortex to the spinal cord, PSA-modified NCAM d oes not become evident until later. When PSA becomes evident, it is re stricted to the distal segment of these axons from the caudal hindbrai n through the spinal cord. The increase in PSA on corticospinal axons coincides with the time that they begin to form collateral branches in the spinal cord. This unique spatiotemporal distribution of PSA sugge sts its involvement in corticospinal axon branching. To test this hypo thesis, PSA was selectively removed by an in vivo injection of endoneu raminidase N. This treatment did not seem to interfere with the pathfi nding of corticospinal axons; however, PSA removal delayed the onset o f collateral branching by corticospinal axons within the spinal cord a nd later diminished the magnitude of branching. These findings indicat e a role for PSA in the regulation of interstitial axon branching, a c rucial step in the process of target recognition and innervation by co rticospinal axons.