Original Research ARTICLE
Differential roles of glycogen synthase kinase 3 subtypes alpha and beta in cortical development
- 1First Affiliated Hospital of Soochow University, China
- 2Korea Institute of Science and Technology, South Korea
Glycogen synthase kinases 3 (GSK3) alpha and beta are expressed in the nervous system, and disruption of GSK3 signaling has been implicated in a wide range of neurodevelopmental and psychiatric disorders. Although several studies have established a role of GSK3 signaling in the nervous system, much less is known about isoform-specific functions. Here, we have examined the role of GSK3 alpha and GSK3 beta in the developing neocortex by performing in utero electroporation with specific siRNAs targeting each isoform. We found that depletion of either GSK3 alpha or GSK3 beta commonly promoted the proliferation of neural progenitor cells in the ventricular zone, but at later stages, knocking down of each isoform resulted in distinct outcomes. In particular, the transformation of radial progenitors to intermediate progenitor cells was promoted in GSK3 alpha-depleted cells, but markedly prevented in GSK3 beta-depleted cells. Moreover, knocking down of GSK3 beta but not GSK3 alpha prevented the generation of upper-layer Cux1+ neurons. Consistent with the distinct outcomes, protein levels of c-Myc and beta-catenin, well-known substrates of GSK3, were differentially affected by depletion of GSK3 alpha and GSK3 beta. Together, these results suggest that GSK3 alpha and GSK3 beta might play distinct roles in the genesis and differentiation of neuronal lineage cells during neocortex development by differential regulation of downstream signaling pathways.
Keywords: kinase, Nervous System, GSK3, development, Cortex
Received: 07 Aug 2017;
Accepted: 09 Nov 2017.
Edited by:Andrei Surguchov, Kansas University of Medical Center Research Institute, United States
Reviewed by:Miroslav Nenov, University of Texas Medical Branch, United States
Jim R. Woodgett, Mount Sinai Hospital, Canada
Copyright: © 2017 Ma, Wang, Chen, Li, Hur and Saijilafu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Prof. Eun-Mi Hur, Korea Institute of Science and Technology, Bongdong-eup, South Korea, email@example.com
Prof. Xxxx Saijilafu, First Affiliated Hospital of Soochow University, Suzhou, China, firstname.lastname@example.org