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The Journal of Neuroscience, June 1, 1999, 19(11):4437-4448

Collapsin-1/Semaphorin-III/D Is Regulated Developmentally in Purkinje Cells and Collapses Pontocerebellar Mossy Fiber Neuronal Growth Cones

Sylvia A. Rabacchi¹, Joanna M. Solowska¹, Barbara Kruk¹, Yuling Luo², Jonathan A. Raper², and Douglas H. Baird¹

¹ Department of Neurobiology and Anatomy, MCP Hahnemann School of Medicine, MCP Hahnemann University, Philadelphia, Pennsylvania 19129, and ² Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

Most axons in the CNS innervate specific subregions or layers of their target regions and form contacts with specific types of target neurons, but the molecular basis of this process is not well understood. To determine whether collapsin-1/semaphorin-III/D, a molecule known to repel specific axons, might guide afferent axons within their cerebellar targets, we characterized its expression by in situ hybridization and observed its effects on mossy and climbing fiber extension and growth cone size in vitro. In newborn mice sema-D is expressed by cerebellar Purkinje cells in parasagittal bands located medially and in some cells of the cerebellar nuclei. Later, sema-D expression in Purkinje cells broadens such that banded expression is no longer prominent, and expression is detected in progressively more lateral regions. By postnatal day 16, expression is observed throughout the cerebellar mediolateral axis.

Collapsin-1 protein, the chick ortholog of sema-D, did not inhibit the extension of neurites from explants of inferior olivary nuclei, the source of climbing fibers that innervate Purkinje cells. In contrast, when it was applied to axons extending from basilar pontine explants, a source of mossy fiber afferents of granule cells, collapsin-1 caused most pontine growth cones to collapse, as evidenced by a reduction in growth cone size of up to 59%. Moreover, 63% of pontine growth cones arrested their extension or retracted. Its effects on mossy fiber extension and its distribution suggest that sema-D prevents mossy fibers from innervating inappropriate cerebellar target regions and cell types.

Key words: cerebellum; mossy fiber; climbing fiber; Purkinje cell; collapsin; semaphorin; basilar pontine nuclei

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Copyright © 1999 Society for Neuroscience  0270-6474/99/19114437-12$05.00/0

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