Fig. 4
Overexpression of RHEB mutants in vivo causes deficits in neuronal migration and seizures in mouse. a, b Representative images of E14.5 in utero electroporated P0 brains (a) or P7 brains (b), with an enlargement showing the migratory pathway of the transfected cells (tdTomato+) from the intermediate zone (IZ) and subplate (SP) to the more superficial layers of the cortex (CP = cortical plate and MZ = marginal zone). c Quantification of the neuronal migration pattern observed in different conditions. Data are presented as mean ± SEM. Statistical significance was assessed by two-way repeated measure ANOVA followed by Bonferroni’s post hoc test (for bins 2–4: *indicates significant difference between control vector and the different RHEB conditions (p < 0.0001); #indicates significant difference between the RHEB-WT and all other conditions (p < 0.0001); for bins 9 and 10: *indicates significant difference between control vector and RHEBp.P37L and RHEBp.S68P; #indicates significant difference between RHEB-WT and RHEBp.P37L and RHEBp.S68P (p < 0.0001)); §indicates significant difference between RHEB-WT and RHEBp.P37L (p < 0.0001); £indicates significant difference between RHEBp.P37L and RHEBp.S68P (p < 0.001). d Kaplan–Meier graph representing onset of tonic–clonic seizures in successfully targeted mice. The insert legends of the graph show N pictures/N mice (c) or N seizure/N total (d)
