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Nat Rev Neurosci. 2010 Aug;11(8):539-51. doi: 10.1038/nrn2870.

GSK3 signalling in neural development.

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Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.


Recent evidence suggests that glycogen synthase kinase 3 (GSK3) proteins and their upstream and downstream regulators have key roles in many fundamental processes during neurodevelopment. Disruption of GSK3 signalling adversely affects brain development and is associated with several neurodevelopmental disorders. Here, we discuss the mechanisms by which GSK3 activity is regulated in the nervous system and provide an overview of the recent advances in the understanding of how GSK3 signalling controls neurogenesis, neuronal polarization and axon growth during brain development. These recent advances suggest that GSK3 is a crucial node that mediates various cellular processes that are controlled by multiple signalling molecules--for example, disrupted in schizophrenia 1 (DISC1), partitioning defective homologue 3 (PAR3), PAR6 and Wnt proteins--that regulate neurodevelopment.

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