The Effect Of Semaphorin4D On The Recovery Following Zebrafish Spinal Cord Injury

Semaphorins comprise a family of proteins involved in axon guidance during development.Semaphorin4D(Sema4D)has both neuroregenerative and neurorepressive functions,being able to stimulate both axonal outgrowth and growth cone collapse during development,and therefore could play an important role in neurological recovery from traumatic injury.Here,we used a zebrafish spinal cord transection model to study the role of Sema4 D in a system capable of neuroregeneration.Real-time qPCR and in situ hybridization showed upregulated Sema4 D expression in the acute response phase(within 3 days post SCI),and downregulated levels in the chronic response phase(11-21 days after SCI).Double-immunostaining for Sema4 D and either Islet-1(motoneuron marker)or Iba-1(microglial marker)showed that microglia surrounded Sema4D-positive motoneurons along the central canal at 4 hours post injury(hpi)and 12 hpi.Following administration of a Sema4 D morpholino to transected zebrafish,anterograde and retrograde tracing indicated that Sema4 D participated in axon regeneration in the spinal cord following SCI in the zebrafish.Swim tracking showed that morpholino-mediated inhibition of Sema4 D retarded the recovery of swimming function when compared to standard control morpholino.The combined results indicate that Sema4 D expression in motoneurons enhances locomotor recovery and axon regeneration,possibly by regulating microglia function,after spinal cord injury in adult zebrafish.