Heparin activates Wnt signaling for neuronal morphogenesis
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Date
2008
Journal Title
Journal ISSN
Volume Title
Publisher
WILEY
Abstract
Writ factors are secreted ligands that affect different aspects of the nervous system behavior like neurodevelopment, synaptogenesis and neurodegeneration. In different model systems, Wnt signaling has been demonstrated to be regulated by heparan sulfate proteoglycans (HSPGs). Whether HSPGs modulate Writ signaling in the context of neuronal behavior is currently unknown. Here we demonstrate that activation of Wnt signaling with the endogenous ligand Wnt-7a results in an increased of neurite outgrowth in the neuroblastoma N2a cell line. Interestingly, heparin induces glycogen synthase kinase-3 beta (GSK-3 beta) inhibition, beta-catenin stabilization and morphological differentiation in both N2a cells and in rat primary hippocampal neuronal cultures. We also show that heparin modulates Wnt-3a-induced stabilization of beta-catenin. Several extracellular matrix and membrane-attached HSPGs were found to be expressed in both in vitro neuronal models. Changes in the expression of specific HSPGs were observed upon differentiation of N2a cells. Taken together, our findings suggest that HSPGs may modulate canonical Writ signaling for neuronal morphogenesis.
Description
Keywords
BETA-PEPTIDE NEUROTOXICITY, NEURITE OUTGROWTH, SULFATE PROTEOGLYCANS, NERVOUS-SYSTEM, HIPPOCAMPAL-NEURONS, SKELETAL-MUSCLE, AXON GUIDANCE, MOLECULAR-CLONING, N-SYNDECAN, PATHWAY