Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Nat Rev Neurosci. 2010 Aug;11(8):539-51. doi: 10.1038/nrn2870.
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.
最近的证据表明,糖原合酶激酶 3(GSK3)蛋白及其上下游调节剂在神经发育过程中的许多基本过程中都起着关键作用。GSK3 信号的破坏会对大脑发育产生不利影响,并与几种神经发育障碍有关。在这里,我们讨论了在神经系统中调节 GSK3 活性的机制,并概述了最近在理解 GSK3 信号如何控制神经发生、神经元极化和轴突生长方面的进展。这些最新进展表明,GSK3 是一个关键节点,介导了多种细胞过程,这些过程受多个信号分子的控制,例如,分裂缺陷同源物 3(PAR3)、PAR6 和 Wnt 蛋白,它们调节神经发育。