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Volume 16, Number 17, Issue of September 1, 1996 pp. 5488-5497
Copyright ©1996 Society for Neuroscience

Spatially Restricted Increase in Polysialic Acid Enhances Corticospinal Axon Branching Related to Target Recognition and Innervation

Received March 20, 1996; revised May 22, 1996; accepted June 12, 1996.

Maryellen M. Daston¹, Martin Bastmeyer¹, Urs Rutishauser², and Dennis D. M. O'Leary¹

¹ Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, California 92037, and ² Department of Genetics and Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106

The polysialic acid (PSA) modification of the neural cell adhesion molecule (NCAM) has been shown to alter the responses of developing axons to their environment. We have studied the potential role of PSA in regulating the innervation of the spinal cord by corticospinal axons, which occurs by a delayed formation of collateral branches from the parent axons. Developmental changes in the distribution of PSA were examined immunohistochemically using light and electron microscopy. Whereas NCAM is distributed along the entire pathway of rat corticospinal axons as they grow from the cortex to the spinal cord, PSA-modified NCAM does not become evident until later. When PSA becomes evident, it is restricted to the distal segment of these axons from the caudal hindbrain 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 suggests its involvement in corticospinal axon branching. To test this hypothesis, PSA was selectively removed by an in vivo injection of endoneuraminidase N. This treatment did not seem to interfere with the pathfinding of corticospinal axons; however, PSA removal delayed the onset of collateral branching by corticospinal axons within the spinal cord and later diminished the magnitude of branching. These findings indicate a role for PSA in the regulation of interstitial axon branching, a crucial step in the process of target recognition and innervation by corticospinal axons.

Key words: axon branching; axon collaterals; axon pathfinding; axon targeting; basilar pons; cell-cell interactions; corticospinal tract; endoneuraminidase N; immunoelectron microscopy; neural cell adhesion molecules; spinal cord

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