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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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Quantification of dendritic branching at P15 in control and Gsk3-deleted neurons.(A) Representitive images of control and Gsk3-deleted neurons used for Sholl analysis with specific processes pseudocolored for identification. (B) Apical dendrite Sholl analysis of Gsk3-deleted neurons shows significantly increased branching close to the soma. p=0.034. Additionally, Gsk3-deleted neurons display a trend toward increased branching in areas further from the soma. (C) Basal dendrite Sholl analysis of Gsk3-deleted neurons shows significantly increased branching in basal dendrites in areas furthest away from the soma (p=0.015). (D) Basal dendrite sholl analysis of dendritic lengths reveals altered morphology of Gsk3-deleted neurons. Gsk3-deleted neurons have increased lengths of basal dendrites in areas beginning 75 μm away from the soma. p=0.023, p=0.0118, and p=0.0202.DOI:http://dx.doi.org/10.7554/eLife.02663.014
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fig5s1: Quantification of dendritic branching at P15 in control and Gsk3-deleted neurons.(A) Representitive images of control and Gsk3-deleted neurons used for Sholl analysis with specific processes pseudocolored for identification. (B) Apical dendrite Sholl analysis of Gsk3-deleted neurons shows significantly increased branching close to the soma. p=0.034. Additionally, Gsk3-deleted neurons display a trend toward increased branching in areas further from the soma. (C) Basal dendrite Sholl analysis of Gsk3-deleted neurons shows significantly increased branching in basal dendrites in areas furthest away from the soma (p=0.015). (D) Basal dendrite sholl analysis of dendritic lengths reveals altered morphology of Gsk3-deleted neurons. Gsk3-deleted neurons have increased lengths of basal dendrites in areas beginning 75 μm away from the soma. p=0.023, p=0.0118, and p=0.0202.DOI:http://dx.doi.org/10.7554/eLife.02663.014

Mentions: As demonstrated above, most Gsk3-deleted neurons failed to migrate and populated the deeper layers of the cortex at P15. Many of these migration arrested neurons exhibited abnormal dendritic arbors (data not shown). Because improper laminar position might affect dendritic arborization, we focused analysis on a small subset of Gsk3-deleted neurons that reached layer 2/3. Images at E16 (Figure 1—figure supplement 1) and E19 (Figure 4A') show that a few Gsk3-deleted neurons are normally positioned and suggest that these normally positioned neurons did not undergo a substantial delay in migration. All of the neurons elaborated dendritic arbors and extended an axon into the corpus callosum. However, many of these normally positioned Gsk3-deleted neurons exhibited markedly abnormally oriented basal dendrites (Figure 5A, arrows). In many cases, basal dendrites were oriented towards the pial surface rather than towards the deeper cortical layers (Figure 5B–D). Additionally, Gsk3-deleted basal processes grew longer and were more branched than those of control neurons (Figure 5D and Figure 5—figure supplement 1C,D). Many Gsk3-deleted neurons also exhibited striking defects in the apical dendrite (Figure 5C,C',E orange arrows and Figure 5—figure supplement 1B). Thus, apical dendrites of the Gsk3-deleted neurons, although properly oriented towards the pial surface often extended branches close to the soma that extended apically rather than laterally (Figure 5E, orange arrows and Figure 5—figure supplement 1B).10.7554/eLife.02663.013Figure 5.GSK-3 signaling is required for proper dendrite orientation.


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)

Quantification of dendritic branching at P15 in control and Gsk3-deleted neurons.(A) Representitive images of control and Gsk3-deleted neurons used for Sholl analysis with specific processes pseudocolored for identification. (B) Apical dendrite Sholl analysis of Gsk3-deleted neurons shows significantly increased branching close to the soma. p=0.034. Additionally, Gsk3-deleted neurons display a trend toward increased branching in areas further from the soma. (C) Basal dendrite Sholl analysis of Gsk3-deleted neurons shows significantly increased branching in basal dendrites in areas furthest away from the soma (p=0.015). (D) Basal dendrite sholl analysis of dendritic lengths reveals altered morphology of Gsk3-deleted neurons. Gsk3-deleted neurons have increased lengths of basal dendrites in areas beginning 75 μm away from the soma. p=0.023, p=0.0118, and p=0.0202.DOI:http://dx.doi.org/10.7554/eLife.02663.014
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Related In: Results  -  Collection

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fig5s1: Quantification of dendritic branching at P15 in control and Gsk3-deleted neurons.(A) Representitive images of control and Gsk3-deleted neurons used for Sholl analysis with specific processes pseudocolored for identification. (B) Apical dendrite Sholl analysis of Gsk3-deleted neurons shows significantly increased branching close to the soma. p=0.034. Additionally, Gsk3-deleted neurons display a trend toward increased branching in areas further from the soma. (C) Basal dendrite Sholl analysis of Gsk3-deleted neurons shows significantly increased branching in basal dendrites in areas furthest away from the soma (p=0.015). (D) Basal dendrite sholl analysis of dendritic lengths reveals altered morphology of Gsk3-deleted neurons. Gsk3-deleted neurons have increased lengths of basal dendrites in areas beginning 75 μm away from the soma. p=0.023, p=0.0118, and p=0.0202.DOI:http://dx.doi.org/10.7554/eLife.02663.014
Mentions: As demonstrated above, most Gsk3-deleted neurons failed to migrate and populated the deeper layers of the cortex at P15. Many of these migration arrested neurons exhibited abnormal dendritic arbors (data not shown). Because improper laminar position might affect dendritic arborization, we focused analysis on a small subset of Gsk3-deleted neurons that reached layer 2/3. Images at E16 (Figure 1—figure supplement 1) and E19 (Figure 4A') show that a few Gsk3-deleted neurons are normally positioned and suggest that these normally positioned neurons did not undergo a substantial delay in migration. All of the neurons elaborated dendritic arbors and extended an axon into the corpus callosum. However, many of these normally positioned Gsk3-deleted neurons exhibited markedly abnormally oriented basal dendrites (Figure 5A, arrows). In many cases, basal dendrites were oriented towards the pial surface rather than towards the deeper cortical layers (Figure 5B–D). Additionally, Gsk3-deleted basal processes grew longer and were more branched than those of control neurons (Figure 5D and Figure 5—figure supplement 1C,D). Many Gsk3-deleted neurons also exhibited striking defects in the apical dendrite (Figure 5C,C',E orange arrows and Figure 5—figure supplement 1B). Thus, apical dendrites of the Gsk3-deleted neurons, although properly oriented towards the pial surface often extended branches close to the soma that extended apically rather than laterally (Figure 5E, orange arrows and Figure 5—figure supplement 1B).10.7554/eLife.02663.013Figure 5.GSK-3 signaling is required for proper dendrite orientation.

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