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Both lipid raft-associated kinases and nonraft fibroblast growth factor (FGF) receptors are implicated in cell adhesion molecule-mediated neurite extension. In the present study, we reveal that \u03b21-mediated neurite outgrowth is abrogated in<jats:italic>Fyn<\/jats:italic>and contactin (<jats:italic>Cntn<\/jats:italic>) null CGNs. \u03b21 protein levels are unchanged in<jats:italic>Fyn<\/jats:italic>null brains, whereas levels are significantly reduced in<jats:italic>Cntn<\/jats:italic>null brain lysates. FGF or EGF (epidermal growth factor) receptor kinase inhibitors have no effect on \u03b21-mediated neurite extension. These results suggest that \u03b21-mediated neurite outgrowth occurs through a lipid raft signaling mechanism that requires the presence of both fyn kinase and contactin.<jats:italic>In vivo<\/jats:italic>,<jats:italic>Scn1b<\/jats:italic>null mice show defective CGN axon extension and fasciculation indicating that \u03b21 plays a role in cerebellar microorganization. In addition, we find that axonal pathfinding and fasciculation are abnormal in corticospinal tracts of<jats:italic>Scn1b<\/jats:italic>null mice consistent with the suggestion that \u03b21 may have widespread effects on postnatal neuronal development. These data are the first to demonstrate a cell-adhesive role for \u03b21<jats:italic>in vivo<\/jats:italic>. We conclude that voltage-gated Na<jats:sup>+<\/jats:sup>channel \u03b21 subunits signal via multiple pathways on multiple timescales and play important roles in the postnatal development of the CNS.<\/jats:p>","DOI":"10.1523\/jneurosci.5446-07.2008","type":"journal-article","created":{"date-parts":[[2008,3,19]],"date-time":"2008-03-19T17:37:08Z","timestamp":1205948228000},"page":"3246-3256","source":"Crossref","is-referenced-by-count":98,"title":["Voltage-Gated Na<sup>+<\/sup>Channel \u03b21 Subunit-Mediated Neurite Outgrowth Requires Fyn Kinase and Contributes to Postnatal CNS Development<i>In Vivo<\/i>"],"prefix":"10.1523","volume":"28","author":[{"given":"William J.","family":"Brackenbury","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tigwa 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