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GSK-3 signaling in developing cortical neurons is essential for radial migration and dendritic orientation.

Morgan-Smith M, Wu Y, Zhu X, Pringle J, Snider WD - Elife (2014)

Bottom Line: Radial migration in hippocampus was similarly affected.GSK-3 regulation of migration in neurons was independent of Wnt/β-catenin signaling.Importantly, phosphorylation of the migration mediator, DCX, at ser327, and phosphorylation of the semaphorin signaling mediator, CRMP-2, at Thr514 were markedly decreased.

View Article: PubMed Central - PubMed

Affiliation: UNC Neuroscience Center, University of North Carolina, Chapel Hill, United States Neurobiology Curriculum, University of North Carolina, Chapel Hill, United States meghan_morgan@med.unc.edu.

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Gsk3-deleted neurons polarize and are highly dynamic.(A) Stage progression analysis of dissociated control and Gsk3-deleted neurons. Stage 1 immature neurons display lamellapodial and filopodial protrusions. Stage 2 neurons have transitioned to form multiple short neurites (multipolar morphology), and stage 3 neurons exhibit a single neurite extending to become an axon (see Dotti et al., 1988). There is no significant delay in polarization (n = 3, 1341 neurons). (B) Live imaging of dissociated Gsk3-deleted neurons reveal dynamic neurites. Images were taken every 11 min. Representative images at time 0 (red), 220 min (blue), and 440 min (green). Merged image is pseudo colored.DOI:http://dx.doi.org/10.7554/eLife.02663.010
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fig4s1: Gsk3-deleted neurons polarize and are highly dynamic.(A) Stage progression analysis of dissociated control and Gsk3-deleted neurons. Stage 1 immature neurons display lamellapodial and filopodial protrusions. Stage 2 neurons have transitioned to form multiple short neurites (multipolar morphology), and stage 3 neurons exhibit a single neurite extending to become an axon (see Dotti et al., 1988). There is no significant delay in polarization (n = 3, 1341 neurons). (B) Live imaging of dissociated Gsk3-deleted neurons reveal dynamic neurites. Images were taken every 11 min. Representative images at time 0 (red), 220 min (blue), and 440 min (green). Merged image is pseudo colored.DOI:http://dx.doi.org/10.7554/eLife.02663.010

Mentions: A number of in vitro studies have suggested that Gsk3 regulates neuronal polarization. It is plausible that some defect or delay in the polarization might account for migration failure. To test this idea, we electroporated Neurod1-Cre and Z/EG into the Gsk3a−/−Gsk3bloxp/loxp cortex, plated cortical cells in dissociated culture and assessed stage progression at 3 days in vitro (3DIV). We observed no statistically significant difference in the stage progression between control and Gsk3-deleted neurons (Figure 4—figure supplement 1A). Further, Gsk3-deleted neurons that successfully extended an axon remained highly dynamic (Figure 4—figure supplement 1B) and extended and retracted neurites. Thus at least some processes that require complex cytoskeletal regulation proceed normally in the Gsk3-deleted neurons.


GSK-3 signaling in developing cortical neurons is essential for radial migration and dendritic orientation.

Morgan-Smith M, Wu Y, Zhu X, Pringle J, Snider WD - Elife (2014)

Gsk3-deleted neurons polarize and are highly dynamic.(A) Stage progression analysis of dissociated control and Gsk3-deleted neurons. Stage 1 immature neurons display lamellapodial and filopodial protrusions. Stage 2 neurons have transitioned to form multiple short neurites (multipolar morphology), and stage 3 neurons exhibit a single neurite extending to become an axon (see Dotti et al., 1988). There is no significant delay in polarization (n = 3, 1341 neurons). (B) Live imaging of dissociated Gsk3-deleted neurons reveal dynamic neurites. Images were taken every 11 min. Representative images at time 0 (red), 220 min (blue), and 440 min (green). Merged image is pseudo colored.DOI:http://dx.doi.org/10.7554/eLife.02663.010
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4109311&req=5

fig4s1: Gsk3-deleted neurons polarize and are highly dynamic.(A) Stage progression analysis of dissociated control and Gsk3-deleted neurons. Stage 1 immature neurons display lamellapodial and filopodial protrusions. Stage 2 neurons have transitioned to form multiple short neurites (multipolar morphology), and stage 3 neurons exhibit a single neurite extending to become an axon (see Dotti et al., 1988). There is no significant delay in polarization (n = 3, 1341 neurons). (B) Live imaging of dissociated Gsk3-deleted neurons reveal dynamic neurites. Images were taken every 11 min. Representative images at time 0 (red), 220 min (blue), and 440 min (green). Merged image is pseudo colored.DOI:http://dx.doi.org/10.7554/eLife.02663.010
Mentions: A number of in vitro studies have suggested that Gsk3 regulates neuronal polarization. It is plausible that some defect or delay in the polarization might account for migration failure. To test this idea, we electroporated Neurod1-Cre and Z/EG into the Gsk3a−/−Gsk3bloxp/loxp cortex, plated cortical cells in dissociated culture and assessed stage progression at 3 days in vitro (3DIV). We observed no statistically significant difference in the stage progression between control and Gsk3-deleted neurons (Figure 4—figure supplement 1A). Further, Gsk3-deleted neurons that successfully extended an axon remained highly dynamic (Figure 4—figure supplement 1B) and extended and retracted neurites. Thus at least some processes that require complex cytoskeletal regulation proceed normally in the Gsk3-deleted neurons.

Bottom Line: Radial migration in hippocampus was similarly affected.GSK-3 regulation of migration in neurons was independent of Wnt/β-catenin signaling.Importantly, phosphorylation of the migration mediator, DCX, at ser327, and phosphorylation of the semaphorin signaling mediator, CRMP-2, at Thr514 were markedly decreased.

View Article: PubMed Central - PubMed

Affiliation: UNC Neuroscience Center, University of North Carolina, Chapel Hill, United States Neurobiology Curriculum, University of North Carolina, Chapel Hill, United States meghan_morgan@med.unc.edu.

Show MeSH
Related in: MedlinePlus