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. 2021 Jul 2;7(27):eabf1973. doi: 10.1126/sciadv.abf1973

Fig. 10. A balance of Cdh6 signaling regulates neuronal orientation.

Fig. 10

(A to C) Cdh6 regulates neuronal orientation through its RGD motif. (A) WT E15.5 animals were in utero electroporated with Cdh6 or an RGD mutant of Cdh6 (Cdh6-RGDmut). (B) GFP+ neurons at P23. Scale bar, 50 μm. (C) Tracings of 10 apical dendrites showing their orientation with respect to the pia. Apical dendrites were superimposed to face the right-hand side of the image. Scale bar, 50 μm. (D to F) Cdh6 is necessary for neuronal orientation. (D) E15.5 WT animals were in utero electroporated with shScr or shCdh6. (E) GFP+ neurons at P23. Scale bar, 50 μm. (F) Tracings of 10 apical dendrites per condition. Scale bar, 50 μm. (G) Average deviation of the apical dendrite for experiments (A to F). N = 25 Cdh6 + shScr cells (from three animals), 53 Cdh6-RGDmut + shScr cells (four animals), 31 shScr cells (seven animals), and 66 shCdh6 cells (five animals). One-way ANOVA (Kruskal-Wallis test) with Dunn’s multiple comparison test. (H) Zeb2 shapes neocortical cytoarchitecture by regulating adhesion at distinct time points of development through repression of Nrp1 and Cdh6. Repression of Nrp1 and downstream integrin signaling by Zeb2 promotes multipolar-bipolar transition and initiation of radial migration. Following migration, Zeb2 regulates Cdh6 expression for correct neuronal orientation. Subsequently, Zeb2 determines dendritic complexity through repression of Nrp1.