Syndecan Promotes Axon Regeneration by Stabilizing Growth Cone Migration

• Regenerating growth cones collapse in syndecan mutants
• Syndecan functions in the injured neuron to stabilize the growth cone
• Syndecan’s core protein, not its sugar chains, mediates growth cone stabilization
• Syndecan also functions in axon guidance via its sugar chains

SummaryGrowth cones facilitate the repair of nervous system damage by providing the driving force for axon regeneration. Using single-neuron laser axotomy and in vivo time-lapse imaging, we show that syndecan, a heparan sulfate (HS) proteoglycan, is required for growth cone function during axon regeneration in C. elegans. In the absence of syndecan, regenerating growth cones form but are unstable and collapse, decreasing the effective growth rate and impeding regrowth to target cells. We provide evidence that syndecan has two distinct functions during axon regeneration: (1) a canonical function in axon guidance that requires expression outside the nervous system and depends on HS chains and (2) an intrinsic function in growth cone stabilization that is mediated by the syndecan core protein, independently of HS. Thus, syndecan is a regulator of a critical choke point in nervous system repair.

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