biostudies-literatureKim WYNINDS NIH HHSNational Institutes of Health981-96https://www.ebi.ac.uk/biostudies/studies/S-EPMC4167845biostudies-literatureUnknown52(6)Glycogen synthase kinase-3beta (GSK-3beta) is thought to mediate morphological responses to a variety of extracellular signals. Surprisingly, we found no gross morphological deficits in nervous system development in GSK-3beta null mice. We therefore designed an shRNA that targeted both GSK-3 isoforms. Strong knockdown of both GSK-3alpha and beta markedly reduced axon growth in dissociated cultures and slice preparations. We then assessed the role of different GSK-3 substrates in regulating axon morphology. Elimination of activity toward primed substrates only using the GSK-3 R96A mutant was associated with a defect in axon polarity (axon branching) compared to an overall reduction in axon growth induced by a kinase-dead mutant. Consistent with this finding, moderate reduction of GSK-3 actiNeuronEssential roles for GSK-3s and GSK-3-primed substrates in neurotrophin-induced and hippocampal axon growth.PMC4167845R01 NS050968R01NS050968Wang YMKaibuchi KAnton ESYokota YKim WYWoodgett JRZhou FQSnider WDZhou JYoshimura TfalseEssential roles for GSK-3s and GSK-3-primed substrates in neurotrophin-induced and hippocampal axon growth.Glycogen synthase kinase-3beta (GSK-3beta) is thought to mediate morphological responses to a variety of extracellular signals. Surprisingly, we found no gross morphological deficits in nervous system development in GSK-3beta null mice. We therefore designed an shRNA that targeted both GSK-3 isoforms. Strong knockdown of both GSK-3alpha and beta markedly reduced axon growth in dissociated cultures and slice preparations. We then assessed the role of different GSK-3 substrates in regulating axon morphology. Elimination of activity toward primed substrates only using the GSK-3 R96A mutant was associated with a defect in axon polarity (axon branching) compared to an overall reduction in axon growth induced by a kinase-dead mutant. Consistent with this finding, moderate reduction of GSK-3 acti2006-01-01T00:00:00Z2006 Dec2025-06-28T03:05:22.773Z2025-06-28T03:05:22.773ZS-EPMC41678451717840210.1016/j.neuron.2006.10.031