Abstract

The Wingless/Integrated (Wnt) signaling pathway plays important roles in central nervous system (CNS) development and regeneration, and β-catenin, the central component, has been considered in association with adult neurogenesis. To decipher its roles on spontaneous spinal cord regeneration, we cloned β-catenin from Gekko japonicus and examined its function in regenerating spinal cord. The protein was localized in the neurons and oligodendrocytes and maintained a stable expression levels during the spinal cord regeneration. The temporal pattern of expression has been found to be completely distinct with those of glycogen synthase kinase 3β (GSK3β). Experiments of gain-of-function by overexpression of full length β-catenin or stabilized ΔN90-β-catenin revealed that the accumulated protein attenuates the elongation of neurites and oligodendrocyte process. Knockdown of endogenous β-catenin, however, decreased proliferation of oligodendrocytes by affecting expression of downstream lef1 and c-jun. The upregulated extracellular matrix fibronectin in injured cord was found to be inefficient in regulation of β-catenin expression. Our results suggest that a tightly regulated stable expression of β-catenin is required for the spontaneous spinal cord regeneration.

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