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Cadherin 2/4 signaling via PTP1B and catenins is crucial for nucleokinesis during radial neuronal migration in the neocortex.

Martinez-Garay I, Gil-Sanz C, Franco SJ, Espinosa A, Molnár Z, Mueller U - Development (2016)

Bottom Line: Surprisingly, perturbation of cadherin-mediated signaling does not affect the formation and extension of leading processes of migrating neocortical neurons.Instead, movement of the cell body and nucleus (nucleokinesis) is disrupted.Taken together, our findings indicate that cadherin-mediated signaling to the cytoskeleton is crucial for nucleokinesis of neocortical projection neurons during their radial migration.

View Article: PubMed Central - PubMed

Affiliation: Molecular and Cellular Neuroscience Department, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USA martinezgarayi@cardiff.ac.uk umueller@scripps.edu.

No MeSH data available.


Related in: MedlinePlus

CDH2 and CDH4 are required for radial migration in mouse cortex. (A) Illustration of the strategy to inactivate Cdh2 and Cdh4 in migrating neurons. Embryos from floxed animals were electroporated in utero at E14.5 with DCX-Cre-i-EGFP or DCX-i-GFP. Position of the electroporated cells was analyzed at E18.5 in the developing somatosensory cortex. (B) Representative images of coronal sections of embryos electroporated as described in A. Electroporated neurons are shown in green and nuclei in blue (TO-PRO). (C) Quantification of the percentage of electroporated neurons that enter the boxed areas in B, representing the upper 25% of the CP. Four animals (Cdh2fl/fl), five animals (Cdh4fl/fl) and six animals (Cdh2/4fl/fl) from three separate experiments were analyzed for each condition. The data represent mean±s.e.m. n.s., non significant, *P<0.01, **P<0.0001, ***P<1×10−13 by Bonferroni post-hoc analysis after one-way ANOVA. MZ, marginal zone; SP, subplate. Scale bar: 100 μm.
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DEV132456F2: CDH2 and CDH4 are required for radial migration in mouse cortex. (A) Illustration of the strategy to inactivate Cdh2 and Cdh4 in migrating neurons. Embryos from floxed animals were electroporated in utero at E14.5 with DCX-Cre-i-EGFP or DCX-i-GFP. Position of the electroporated cells was analyzed at E18.5 in the developing somatosensory cortex. (B) Representative images of coronal sections of embryos electroporated as described in A. Electroporated neurons are shown in green and nuclei in blue (TO-PRO). (C) Quantification of the percentage of electroporated neurons that enter the boxed areas in B, representing the upper 25% of the CP. Four animals (Cdh2fl/fl), five animals (Cdh4fl/fl) and six animals (Cdh2/4fl/fl) from three separate experiments were analyzed for each condition. The data represent mean±s.e.m. n.s., non significant, *P<0.01, **P<0.0001, ***P<1×10−13 by Bonferroni post-hoc analysis after one-way ANOVA. MZ, marginal zone; SP, subplate. Scale bar: 100 μm.

Mentions: To determine the extent to which CDH2 and CDH4 regulate radial migration, we obtained mice carrying a floxed allele of Cdh2 (Kostetskii et al., 2005). We also generated mice carrying a floxed allele of Cdh4 (Fig. S3). We used in utero electroporation to introduce a plasmid expressing Cre recombinase and EGFP into embryos carrying floxed alleles for Cdh2 and Cdh4 (Fig. 2A). Expression of Cre and EGFP were controlled by a doublecortin (DCX) promoter, which is active in migrating neurons but not in RGCs (Franco et al., 2011; Wang et al., 2007). This allowed us to address the cell-autonomous functions of Cdh2 and Cdh4 in migrating neurons and to prevent disruption of adherens junctions between RGCs that are formed by CDH2 (Kadowaki et al., 2007).Fig. 2.


Cadherin 2/4 signaling via PTP1B and catenins is crucial for nucleokinesis during radial neuronal migration in the neocortex.

Martinez-Garay I, Gil-Sanz C, Franco SJ, Espinosa A, Molnár Z, Mueller U - Development (2016)

CDH2 and CDH4 are required for radial migration in mouse cortex. (A) Illustration of the strategy to inactivate Cdh2 and Cdh4 in migrating neurons. Embryos from floxed animals were electroporated in utero at E14.5 with DCX-Cre-i-EGFP or DCX-i-GFP. Position of the electroporated cells was analyzed at E18.5 in the developing somatosensory cortex. (B) Representative images of coronal sections of embryos electroporated as described in A. Electroporated neurons are shown in green and nuclei in blue (TO-PRO). (C) Quantification of the percentage of electroporated neurons that enter the boxed areas in B, representing the upper 25% of the CP. Four animals (Cdh2fl/fl), five animals (Cdh4fl/fl) and six animals (Cdh2/4fl/fl) from three separate experiments were analyzed for each condition. The data represent mean±s.e.m. n.s., non significant, *P<0.01, **P<0.0001, ***P<1×10−13 by Bonferroni post-hoc analysis after one-way ANOVA. MZ, marginal zone; SP, subplate. Scale bar: 100 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4920171&req=5

DEV132456F2: CDH2 and CDH4 are required for radial migration in mouse cortex. (A) Illustration of the strategy to inactivate Cdh2 and Cdh4 in migrating neurons. Embryos from floxed animals were electroporated in utero at E14.5 with DCX-Cre-i-EGFP or DCX-i-GFP. Position of the electroporated cells was analyzed at E18.5 in the developing somatosensory cortex. (B) Representative images of coronal sections of embryos electroporated as described in A. Electroporated neurons are shown in green and nuclei in blue (TO-PRO). (C) Quantification of the percentage of electroporated neurons that enter the boxed areas in B, representing the upper 25% of the CP. Four animals (Cdh2fl/fl), five animals (Cdh4fl/fl) and six animals (Cdh2/4fl/fl) from three separate experiments were analyzed for each condition. The data represent mean±s.e.m. n.s., non significant, *P<0.01, **P<0.0001, ***P<1×10−13 by Bonferroni post-hoc analysis after one-way ANOVA. MZ, marginal zone; SP, subplate. Scale bar: 100 μm.
Mentions: To determine the extent to which CDH2 and CDH4 regulate radial migration, we obtained mice carrying a floxed allele of Cdh2 (Kostetskii et al., 2005). We also generated mice carrying a floxed allele of Cdh4 (Fig. S3). We used in utero electroporation to introduce a plasmid expressing Cre recombinase and EGFP into embryos carrying floxed alleles for Cdh2 and Cdh4 (Fig. 2A). Expression of Cre and EGFP were controlled by a doublecortin (DCX) promoter, which is active in migrating neurons but not in RGCs (Franco et al., 2011; Wang et al., 2007). This allowed us to address the cell-autonomous functions of Cdh2 and Cdh4 in migrating neurons and to prevent disruption of adherens junctions between RGCs that are formed by CDH2 (Kadowaki et al., 2007).Fig. 2.

Bottom Line: Surprisingly, perturbation of cadherin-mediated signaling does not affect the formation and extension of leading processes of migrating neocortical neurons.Instead, movement of the cell body and nucleus (nucleokinesis) is disrupted.Taken together, our findings indicate that cadherin-mediated signaling to the cytoskeleton is crucial for nucleokinesis of neocortical projection neurons during their radial migration.

View Article: PubMed Central - PubMed

Affiliation: Molecular and Cellular Neuroscience Department, Dorris Neuroscience Center, The Scripps Research Institute, La Jolla, CA 92037, USA martinezgarayi@cardiff.ac.uk umueller@scripps.edu.

No MeSH data available.


Related in: MedlinePlus